{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:28:44Z","timestamp":1787218124193,"version":"build-2736575974"},"reference-count":141,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016694","name":"Science and Technology Development Plan of Shandong Province","doi-asserted-by":"publisher","award":["202403070867"],"award-info":[{"award-number":["202403070867"]}],"id":[{"id":"10.13039\/100016694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014761","name":"Natural Science Foundation of Qingdao Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014761","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Interleukin-34 (IL-34) is a brain-enriched cytokine and a tissue-restricted ligand of colony-stimulating factor-1 receptor (CSF-1R) that plays an important role in microglial development, survival, and functional specialization. A growing body of evidence indicates that IL-34 is dysregulated in both central and peripheral nervous system diseases and exerts pleiotropic effects not only through CSF-1R but also through non-canonical receptors, including TREM2, syndecan-1, and PTP-\u03b6. Under physiological conditions, IL-34 is constitutively produced predominantly by neurons across both the central and peripheral nervous systems. However, in pathological settings, its cellular sources expand dynamically: in CNS diseases, IL-34 is primarily derived from stressed neurons and reactive astrocytes, whereas in PNS disorders, it is robustly upregulated by injured sensory neurons, satellite glial cells, and reactive Schwann cells. IL-34 contributes to the regulation of resident glia in the CNS, while evidence from peripheral immune disorders suggests that it may also influence infiltrating myeloid-cell adaptation under pathological conditions. In this review, we highlight the multiple effects of IL-34 and its receptor network on CNS-resident, peripheral glial, and peripheral immune cells, with particular attention to the available data supporting its dual role in neuroprotection and inflammatory amplification. We synthesize recent findings regarding IL-34\u2019s role in myeloid reprogramming, particularly in orchestrating transcriptional and functional phenotypic shifts. While current literature provides evidence linking IL-34 to these transcriptional changes, its contribution to metabolic and epigenetic remodeling remains an emerging field. Furthermore, our findings summarized in this manuscript may help evaluate whether targeting IL-34-related pathways can be exploited for therapeutic intervention in neurodevelopmental, neurodegenerative, cerebrovascular, and peripheral nerve pathologies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1898176","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:22:31Z","timestamp":1787217751000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Roles of IL-34 in neurological diseases: neuroprotection, inflammatory regulation, and myeloid plasticity"],"prefix":"10.3389","volume":"17","author":[{"given":"Yilong","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuewen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Qingdao Women and Children's Hospital","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2021.101517","article-title":"Il-34, the rationale for its expression in physiological and pathological conditions","volume":"54","author":"Otsuka","year":"2021","journal-title":"Semin Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2360","article-title":"Il-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia","volume":"13","author":"Wang","year":"2012","journal-title":"Nat Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.11.001","article-title":"Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia","volume":"37","author":"Greter","year":"2012","journal-title":"Immunity"},{"key":"B5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.coi.2005.11.006","article-title":"Colony-stimulating factor-1 in immunity and inflammation","volume":"18","author":"Chitu","year":"2006","journal-title":"Curr Opin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021857","article-title":"Csf-1 receptor signaling in myeloid cells","volume":"6","author":"Stanley","year":"2014","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/science.1154370","article-title":"Discovery of a cytokine and its receptor by functional screening of the extracellular proteome","volume":"320","author":"Lin","year":"2008","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0909624","article-title":"Pivotal advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products","volume":"87","author":"Garceau","year":"2010","journal-title":"J Leukoc Biol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1189\/jlb.1209822","article-title":"Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells","volume":"88","author":"Wei","year":"2010","journal-title":"J Leukoc Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02195-7","article-title":"Mutations in the human CSF1R gene impact microglia's maintenance of brain white matter integrity","volume":"26","author":"Du","year":"2025","journal-title":"Nat Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1016\/j.immuni.2025.06.002","article-title":"Excitatory-neuron-derived interleukin-34 supports cortical developmental microglia function","volume":"58","author":"Devlin","year":"2025","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2026.01.032","article-title":"Brain-engrafted monocyte-derived macrophages from blood and skull-bone marrow exhibit distinct properties","volume":"114","author":"Du","year":"2026","journal-title":"Neuron"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb2119","article-title":"Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke","volume":"6","author":"Chen","year":"2020","journal-title":"Sci Adv"},{"key":"B14","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.ccell.2024.05.001","article-title":"Distinct roles of TREM2 in central nervous system cancers and peripheral cancers","volume":"42","author":"Zhong","year":"2024","journal-title":"Cancer Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1186\/s12967-025-06799-3","article-title":"TREM2-mediated regulation of microglial activity: a promising target for the treatment of ischemic stroke","volume":"23","author":"Yu","year":"2025","journal-title":"J Transl Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A unique microglia type associated with restricting development of Alzheimer's disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022018619","article-title":"TREM2 acts as a receptor for IL-34 to suppress acute myeloid leukemia in mice","volume":"141","author":"Xie","year":"2023","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251320418","article-title":"Il-34\/TREM2 modulates microglia-mediated inflammation and provides neuroprotection in a mouse model of sporadic Alzheimer's disease","volume":"104","author":"Wang","year":"2025","journal-title":"J Alzheimers Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00039.2022","article-title":"Syndecan-1 in liver pathophysiology","volume":"323","author":"Reszegi","year":"2022","journal-title":"Am J Physiol Cell Physiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s00251-024-01366-4","article-title":"Syndecan-1: a key player in health and disease","volume":"77","author":"Diab","year":"2024","journal-title":"Immunogenetics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2025.104997","article-title":"Glycocalyx shedding as a clinical biomarker in critical illness","volume":"144","author":"Inoda","year":"2025","journal-title":"Exp Mol Pathol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300931","article-title":"Syndecan-1, a cell surface proteoglycan, negatively regulates initial leukocyte recruitment to the brain across the choroid plexus in murine experimental autoimmune encephalomyelitis","volume":"191","author":"Zhang","year":"2013","journal-title":"J Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042883","article-title":"The niche factor syndecan-1 regulates the maintenance and proliferation of neural progenitor cells during mammalian cortical development","volume":"7","author":"Wang","year":"2012","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1212\/nxi.0000000000200230","article-title":"Cd138 as a specific CSF biomarker of multiple sclerosis","volume":"11","author":"Hinsinger","year":"2024","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B25","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1097\/shk.0000000000002255","article-title":"Clinical value of syndecan-1 levels in trauma brain injury: a meta-analysis","volume":"61","author":"Xie","year":"2024","journal-title":"Shock"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.01.023","article-title":"Syndecan-1 regulates the biological activities of interleukin-34","volume":"1853","author":"Segaliny","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e33791","article-title":"Il-34 and its receptors as predictors of brain metastasis and prognosis in lung adenocarcinoma: unveiling insights through bioinformatic and immunohistochemical investigations","volume":"10","author":"Geng","year":"2024","journal-title":"Heliyon"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/art.41792","article-title":"Interleukin-34 reprograms glycolytic and osteoclastic rheumatoid arthritis macrophages via syndecan 1 and macrophage colony-stimulating factor receptor","volume":"73","author":"Van Raemdonck","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2023.156348","article-title":"Role of IL-34 and its receptors in inflammatory diseases","volume":"171","author":"Shang","year":"2023","journal-title":"Cytokine"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m112.442731","article-title":"Receptor-type protein-tyrosine phosphatase \u03b6 is a functional receptor for interleukin-34","volume":"288","author":"Nandi","year":"2013","journal-title":"J Biol Chem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.35070","article-title":"Immunomodulation of interleukin-34 and its potential significance as a disease biomarker and therapeutic target","volume":"15","author":"Ge","year":"2019","journal-title":"Int J Biol Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0245340","article-title":"Reno-protective effect of IL-34 inhibition on cisplatin-induced nephrotoxicity in mice","volume":"16","author":"Wada","year":"2021","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/bjd\/ljaf130","article-title":"Interleukin (IL)-34 promotes the inflammatory role of IL-1\u03b2-producing myeloid cells in pemphigus lesions","volume":"193","author":"Huang","year":"2025","journal-title":"Br J Dermatol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3746-y","article-title":"Increased IL-6 expression on THP-1 by IL-34 stimulation up-regulated rheumatoid arthritis Th17 cells","volume":"37","author":"Wang","year":"2018","journal-title":"Clin Rheumatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081665","article-title":"The newly discovered cytokine IL-34 is expressed in gingival fibroblasts, shows enhanced expression by pro-inflammatory cytokines, and stimulates osteoclast differentiation","volume":"8","author":"Bostr\u00f6m","year":"2013","journal-title":"PloS One"},{"key":"B36","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/s41598-017-18433-4","article-title":"Il-34 and CSF-1 display an equivalent macrophage differentiation ability but a different polarization potential","volume":"8","author":"Boulakirba","year":"2018","journal-title":"Sci Rep"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.579000","article-title":"Inhibition of IL-34 unveils tissue-selectivity and is sufficient to reduce microglial proliferation in a model of chronic neurodegeneration","volume":"11","author":"Obst","year":"2020","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2025.07.005","article-title":"Border-associated macrophages: guardians of vascular homeostasis","volume":"46","author":"Xing","year":"2025","journal-title":"Trends Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.04.005","article-title":"Border-associated macrophages as gatekeepers of brain homeostasis and immunity","volume":"58","author":"Vara-P\u00e9rez","year":"2025","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: a field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8670","article-title":"Microglia development follows a stepwise program to regulate brain homeostasis","volume":"353","author":"Matcovitch-Natan","year":"2016","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1515\/nf-2005-0304","article-title":"Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo","volume":"308","author":"Nimmerjahn","year":"2005","journal-title":"Science"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034406","article-title":"Microglia in physiology and disease","volume":"79","author":"Wolf","year":"2017","journal-title":"Annu Rev Physiol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10896","article-title":"Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia","volume":"95","author":"Harrison","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19030831","article-title":"The role of macrophages in neuroinflammatory and neurodegenerative pathways of Alzheimer\u2019s disease, amyotrophic lateral sclerosis, and multiple sclerosis: pathogenetic cellular effectors and potential therapeutic targets","volume":"19","author":"Mammana","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B46","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.celrep.2016.12.041","article-title":"Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain","volume":"18","author":"Askew","year":"2017","journal-title":"Cell Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/science.1194637","article-title":"Fate mapping analysis reveals that adult microglia derive from primitive macrophages","volume":"330","author":"Ginhoux","year":"2010","journal-title":"Science"},{"key":"B48","doi-asserted-by":"publisher","first-page":"4046","DOI":"10.1038\/ncomms5046","article-title":"Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia","volume":"5","author":"Mazaheri","year":"2014","journal-title":"Nat Commun"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.08.014","article-title":"Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis","volume":"7","author":"Sierra","year":"2010","journal-title":"Cell Stem Cell"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132528","article-title":"Microglial physiology: unique stimuli, specialized responses","volume":"27","author":"Ransohoff","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-23","article-title":"Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer's disease","volume":"5","author":"Jin","year":"2008","journal-title":"J Neuroinflamm"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl249","article-title":"Role of toll-like receptor signalling in Abeta uptake and clearance","volume":"129","author":"Tahara","year":"2006","journal-title":"Brain"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/nature11729","article-title":"NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP\/PS1 mice","volume":"493","author":"Heneka","year":"2013","journal-title":"Nature"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201743922","article-title":"TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury","volume":"18","author":"Mazaheri","year":"2017","journal-title":"EMBO Rep"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1172\/jci77983","article-title":"TREM2 sustains microglial expansion during aging and response to demyelination","volume":"125","author":"Poliani","year":"2015","journal-title":"J Clin Invest"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2459-16.2017","article-title":"TREM2 promotes microglial survival by activating Wnt\/\u03b2-catenin pathway","volume":"37","author":"Zheng","year":"2017","journal-title":"J Neurosci"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.06.015","article-title":"TREM2 binds to apolipoproteins, including APOE and CLU\/APOJ, and thereby facilitates uptake of amyloid-beta by microglia","volume":"91","author":"Yeh","year":"2016","journal-title":"Neuron"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.049","article-title":"TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model","volume":"160","author":"Wang","year":"2015","journal-title":"Cell"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.07.004","article-title":"Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation","volume":"13","author":"Song","year":"2017","journal-title":"Alzheimers Dement"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-308883.7","article-title":"TREM2 variants in Alzheimer's disease","volume":"368","author":"Guerreiro","year":"2013","journal-title":"N Engl J Med"},{"key":"B61","doi-asserted-by":"publisher","first-page":"493","DOI":"10.3233\/jpd-130250","article-title":"The role of innate and adaptive immunity in Parkinson's disease","volume":"3","author":"Kannarkat","year":"2013","journal-title":"J Parkinsons Dis"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02268-5","article-title":"Periphery and brain, innate and adaptive immunity in Parkinson's disease","volume":"141","author":"Harms","year":"2021","journal-title":"Acta Neuropathol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(87)90252-9","article-title":"Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains","volume":"38","author":"McGeer","year":"1988","journal-title":"Neurology"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05087.x","article-title":"Nitrated alpha-synuclein-activated microglial profiling for Parkinson's disease","volume":"104","author":"Reynolds","year":"2008","journal-title":"J Neurochem"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.021","article-title":"Multiple sclerosis: mechanisms and immunotherapy","volume":"97","author":"Baecher-Allan","year":"2018","journal-title":"Neuron"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.06.023","article-title":"Microglia in multiple sclerosis: Protectors turn destroyers","volume":"110","author":"Yong","year":"2022","journal-title":"Neuron"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0184-2","article-title":"The pro-remyelination properties of microglia in the central nervous system","volume":"15","author":"Lloyd","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1038\/s41467-021-22532-2","article-title":"Microglial neuropilin-1 promotes oligodendrocyte expansion during development and remyelination by trans-activating platelet-derived growth factor receptor","volume":"12","author":"Sherafat","year":"2021","journal-title":"Nat Commun"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141656","article-title":"Inefficient clearance of myelin debris by microglia impairs remyelinating processes","volume":"212","author":"Lampron","year":"2015","journal-title":"J Exp Med"},{"key":"B71","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1007\/s00401-020-02129-7","article-title":"Niacin-mediated rejuvenation of macrophage\/microglia enhances remyelination of the aging central nervous system","volume":"139","author":"Rawji","year":"2020","journal-title":"Acta Neuropathol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190812","article-title":"CNS-localized myeloid cells capture living invading T cells during neuroinflammation","volume":"217","author":"Wasser","year":"2020","journal-title":"J Exp Med"},{"key":"B73","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.expneurol.2018.05.021","article-title":"Csf1R inhibition attenuates experimental autoimmune encephalomyelitis and promotes recovery","volume":"307","author":"Nissen","year":"2018","journal-title":"Exp Neurol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/s41419-020-03084-7","article-title":"CSF1R signaling is a regulator of pathogenesis in progressive MS","volume":"11","author":"Hagan","year":"2020","journal-title":"Cell Death Dis"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-3","article-title":"Amyotrophic lateral sclerosis","volume":"4","author":"Wijesekera","year":"2009","journal-title":"Orphanet J Rare Dis"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(18)30394-6","article-title":"Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies","volume":"18","author":"Beers","year":"2019","journal-title":"Lancet Neurol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10465","article-title":"ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function","volume":"7","author":"Sharma","year":"2016","journal-title":"Nat Commun"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1126\/science.1154584","article-title":"TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis","volume":"319","author":"Sreedharan","year":"2008","journal-title":"Science"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0329-3","article-title":"Protective and toxic neuroinflammation in amyotrophic lateral sclerosis","volume":"12","author":"Hooten","year":"2015","journal-title":"Neurotherapeutics"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1111\/joa.13484","article-title":"Peripheral glia diversity","volume":"241","author":"Reed","year":"2022","journal-title":"J Anat"},{"key":"B81","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/cells14010047","article-title":"Schwann cells in neuromuscular disorders: A spotlight on amyotrophic lateral sclerosis","volume":"14","author":"Moss","year":"2025","journal-title":"Cells"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1007\/bf00308818","article-title":"Sensory nerve pathology in amyotrophic lateral sclerosis","volume":"82","author":"Heads","year":"1991","journal-title":"Acta Neuropathol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.05.014","article-title":"Selective knockdown of mutant SOD1 in Schwann cells ameliorates disease in G85R mutant SOD1 transgenic mice","volume":"48","author":"Wang","year":"2012","journal-title":"Neurobiol Dis"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.32.5.1208","article-title":"Enhanced expression of Iba1, ionized calcium-binding adapter molecule 1, after transient focal cerebral ischemia in rat brain","volume":"32","author":"Ito","year":"2001","journal-title":"Stroke"},{"key":"B85","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s12974-019-1516-2","article-title":"Neuroinflammation: friend and foe for ischemic stroke","volume":"16","author":"Jayaraj","year":"2019","journal-title":"J Neuroinflamm"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13139","article-title":"Microglial M1\/M2 polarization and metabolic states","volume":"173","author":"Orihuela","year":"2016","journal-title":"Br J Pharmacol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1177\/1073858416639005","article-title":"Tumor necrosis factor and stroke: role of the blood-brain barrier","volume":"83","author":"Pan","year":"2007","journal-title":"Prog Neurobiol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24009","article-title":"Microglia-mediated phagocytosis of apoptotic nuclei is impaired in the adult murine hippocampus after stroke","volume":"69","author":"Rudolph","year":"2021","journal-title":"Glia"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.112.659656","article-title":"Microglia\/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia","volume":"43","author":"Hu","year":"2012","journal-title":"Stroke"},{"key":"B90","doi-asserted-by":"publisher","first-page":"12221","DOI":"10.1038\/s41598-019-48759-0","article-title":"Isosteviol sodium protects against ischemic stroke by modulating microglia\/macrophage polarization via disruption of GAS5\/miR-146a-5p sponge","volume":"9","author":"Zhang","year":"2019","journal-title":"Sci Rep"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.117.018505","article-title":"Fingolimod protects against ischemic white matter damage by modulating microglia toward M2 polarization via STAT3 pathway","volume":"48","author":"Qin","year":"2017","journal-title":"Stroke"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.7150\/thno.27882","article-title":"Microglial TLR4-dependent autophagy induces ischemic white matter damage via STAT1\/6 pathway","volume":"8","author":"Qin","year":"2018","journal-title":"Theranostics"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.967825","article-title":"TREM2 improves neurological dysfunction and attenuates neuroinflammation, TLR signaling and neuronal apoptosis in the acute phase of intracerebral hemorrhage","volume":"14","author":"Liu","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-093019-110159","article-title":"Microglia and central nervous system-associated macrophages-from origin to disease modulation","volume":"39","author":"Prinz","year":"2021","journal-title":"Annu Rev Immunol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/341308","article-title":"Current concept and update of the macrophage plasticity concept: Intracellular mechanisms of reprogramming and M3 macrophage \"switch\" phenotype","volume":"2015","author":"Malyshev","year":"2015","journal-title":"BioMed Res Int"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.010","article-title":"Microglia heterogeneity in the single-cell era","volume":"30","author":"Masuda","year":"2020","journal-title":"Cell Rep"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.003","article-title":"Disease-associated microglia: A universal immune sensor of neurodegeneration","volume":"173","author":"Deczkowska","year":"2018","journal-title":"Cell"},{"key":"B98","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1126\/science.aat7554","article-title":"Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation","volume":"14","author":"Jord\u00e3o","year":"2019","journal-title":"Science"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2013.04.019","article-title":"Transcriptional profiling and pathway analysis of CSF-1 and IL-34 effects on human monocyte differentiation","volume":"63","author":"Barve","year":"2013","journal-title":"Cytokine"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-026-01741-7","article-title":"Genetic-environmental programming of microglial identity: Shaping spatiotemporal dynamics in neurodevelopment and neurodevelopmental diseases","author":"Zhang","year":"2026","journal-title":"Cell Mol Neurobiol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0023-4","article-title":"Innate immune memory in the brain shapes neurological disease hallmarks","volume":"556","author":"Wendeln","year":"2018","journal-title":"Nature"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23787","article-title":"Epigenomic and transcriptional determinants of microglial cell identity","volume":"68","author":"Gosselin","year":"2020","journal-title":"Glia"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adn3963","article-title":"Intestinal epithelium-derived IL-34 reprograms macrophages to mitigate gastrointestinal tract graft-versus-host disease","volume":"17","author":"Rayasam","year":"2025","journal-title":"Sci Transl Med"},{"key":"B104","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.neuron.2017.03.042","article-title":"iPSC-derived human microglia-like cells to study neurological diseases","volume":"94","author":"Abud","year":"2017","journal-title":"Neuron"},{"key":"B105","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s13024-018-0297-x","article-title":"Development and validation of a simplified method to generate human microglia from pluripotent stem cells","volume":"13","author":"McQuade","year":"2018","journal-title":"Mol Neurodegener"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2024.103990","article-title":"Microglia-like cells from patient monocytes demonstrate increased phagocytic activity in probable Alzheimer's disease","volume":"132","author":"Gonul","year":"2025","journal-title":"Mol Cell Neurosci"},{"key":"B107","doi-asserted-by":"publisher","first-page":"115909","DOI":"10.2139\/ssrn.5009356","article-title":"Cytokine-induced reprogramming of human macrophages toward Alzheimer's disease-relevant molecular and cellular phenotypes in vitro","volume":"44","author":"Podle\u015bny-Drabiniok","year":"2025","journal-title":"Cell Rep"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.3233\/978-1-61499-876-1-609","article-title":"Role of amyloid-\u03b2 and tau proteins in Alzheimer's disease: Confuting the amyloid cascade","volume":"64","author":"Gulisano","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02263-w","article-title":"Distinct amyloid-\u03b2 and tau-associated microglia profiles in Alzheimer's disease","volume":"141","author":"Gerrits","year":"2021","journal-title":"Acta Neuropathol"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.06.011","article-title":"Interleukin-34 selectively enhances the neuroprotective effects of microglia to attenuate oligomeric amyloid-\u03b2 neurotoxicity","volume":"179","author":"Mizuno","year":"2011","journal-title":"Am J Pathol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115435","article-title":"IL-34 exacerbates pathogenic features of Alzheimer's disease and calvaria osteolysis in triple transgenic (3x-Tg) female mice","volume":"166","author":"Ho","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00244","article-title":"Studies on colony stimulating factor receptor-1 and ligands colony stimulating factor-1 and interleukin-34 in Alzheimer's disease brains and human microglia","volume":"9","author":"Walker","year":"2017","journal-title":"Front Aging Neurosci"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01449","article-title":"Effects of IL-34 on macrophage immunological profile in response to Alzheimer's-related A\u03b2(42) assemblies","volume":"11","author":"Zuroff","year":"2020","journal-title":"Front Immunol"},{"key":"B114","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s00784-025-06376-4","article-title":"Elevated levels of salivary interleukin-34 in patients suffering from Alzheimer's disease","volume":"29","author":"Clark","year":"2025","journal-title":"Clin Oral Investig"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12782","article-title":"Dysfunction of the blood-brain barrier in Alzheimer's disease: Evidence from human studies","volume":"48","author":"Kurz","year":"2022","journal-title":"Neuropathol Appl Neurobiol"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.178297","article-title":"From plasma proteomics Mendelian randomization to neuropathological validation: The potential role of CTSH-GRN-TMEM106B and TREM2-IL-34 networks of microglia in Alzheimer's disease","volume":"1007","author":"Yuan","year":"2025","journal-title":"Eur J Pharmacol"},{"key":"B117","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1186\/s13195-024-01609-2","article-title":"Molecular landscape of the overlap between Alzheimer's disease and somatic insulin-related diseases","volume":"16","author":"Ruisch","year":"2024","journal-title":"Alzheimers Res Ther"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.139394","article-title":"Identification of potential therapeutic targets for Alzheimer's disease from the proteomes of plasma and cerebrospinal fluid in a multicenter Mendelian randomization study","volume":"294","author":"Wang","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-022-00934-6","article-title":"Parkinson's disease: A multisystem disorder","volume":"39","author":"Costa","year":"2023","journal-title":"Neurosci Bull"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu Rev Immunol"},{"key":"B121","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.cellimm.2018.02.011","article-title":"Interleukin-1\u03b2, interleukin-1 receptor antagonist, interleukin-6, interleukin-10, and tumor necrosis factor-\u03b1 levels in CSF and serum in relation to the clinical diversity of Parkinson's disease","volume":"327","author":"Karpenko","year":"2018","journal-title":"Cell Immunol"},{"key":"B122","doi-asserted-by":"publisher","first-page":"8421","DOI":"10.3390\/ijms21228421","article-title":"Neurodegeneration and inflammation-an interesting interplay in Parkinson's disease","volume":"21","author":"Marogianni","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.09.129","article-title":"Suppression of neuroinflammation by matrix metalloproteinase-8 inhibitor in aged normal and LRRK2 G2019S Parkinson's disease model mice challenged with lipopolysaccharide","volume":"493","author":"Kim","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww258","article-title":"Progressive multiple sclerosis: From pathogenic mechanisms to treatment","volume":"140","author":"Correale","year":"2017","journal-title":"Brain"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81227","article-title":"IL-34 is a Treg-specific cytokine and mediates transplant tolerance","volume":"125","author":"B\u00e9zie","year":"2015","journal-title":"J Clin Invest"},{"key":"B126","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s13045-025-01735-w","article-title":"Immunosenescence and cancer: Molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges","volume":"18","author":"Liu","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2111804119","article-title":"CSF-1 maintains pathogenic but not homeostatic myeloid cells in the central nervous system during autoimmune neuroinflammation","volume":"119","author":"Hwang","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"B128","doi-asserted-by":"publisher","first-page":"106150","DOI":"10.1016\/j.msard.2024.106150","article-title":"Is there a relationship between CSF interleukin 34 level and clinicoradiological activity and IgG index in patients with MS","volume":"92","author":"G\u00f6k\u00e7e","year":"2024","journal-title":"Mult Scler Relat Disord"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577652","article-title":"Increased serum interleukin-34 levels as a novel diagnostic and prognostic biomarker in patients with acute ischemic stroke","volume":"358","author":"Huang","year":"2021","journal-title":"J Neuroimmunol"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.29271\/jcpsp.2025.08.1065","article-title":"Correlation between cystatin-C and interleukin-34 expression detection and post-stroke cognitive impairment","volume":"35","author":"Wang","year":"2025","journal-title":"J Coll Physicians Surg Pak"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.2174\/1567202618666211110113323","article-title":"Association of serum interleukin-34 and insulin resistance with cognitive impairment in patients with cerebral small vessel disease","volume":"18","author":"Jiang","year":"2021","journal-title":"Curr Neurovasc Res"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6793860","article-title":"Decreased levels of serum IL-34 associated with cognitive impairment in vascular dementia","volume":"2021","author":"Wang","year":"2021","journal-title":"BioMed Res Int"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx315","article-title":"IKK\u03b2 and mutant huntingtin interactions regulate the expression of IL-34: Implications for microglial-mediated neurodegeneration in HD","volume":"26","author":"Khoshnan","year":"2017","journal-title":"Hum Mol Genet"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1038\/nature18283","article-title":"A complement-microglial axis drives synapse loss during virus-induced memory impairment","volume":"534","author":"Vasek","year":"2016","journal-title":"Nature"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23768","article-title":"Schwann cells orchestrate peripheral nerve inflammation through the expression of CSF1, IL-34, and SCF in amyotrophic lateral sclerosis","volume":"68","author":"Trias","year":"2020","journal-title":"Glia"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14657","article-title":"Stigmasterol alleviates neuropathic pain by reducing Schwann cell-macrophage cascade in DRG by modulating IL-34\/CSF1R","volume":"30","author":"Si","year":"2024","journal-title":"CNS Neurosci Ther"},{"key":"B137","doi-asserted-by":"publisher","first-page":"3964","DOI":"10.3390\/ijms26093964","article-title":"Paeonol relieves chronic neuropathic pain by reducing communication between Schwann cells and macrophages in the dorsal root ganglia after injury","volume":"26","author":"Li","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03876-w","article-title":"(+)-Catechin alleviates CCI-induced neuropathic pain in rats by modulating the IL34\/CSFIR axis and attenuating the Schwann cell-macrophage cascade response in the DRG","volume":"61","author":"Jing","year":"2024","journal-title":"Mol Neurobiol"},{"key":"B139","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.3390\/cancers16173055","article-title":"CSF1R ligands expressed by murine gliomas promote M-MDSCs to suppress CD8(+) T cells in a NOS-dependent manner","volume":"16","author":"Takacs","year":"2024","journal-title":"Cancers (Basel)"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02019","article-title":"Function of CSF1 and IL34 in macrophage homeostasis, inflammation, and cancer","volume":"10","author":"Lin","year":"2019","journal-title":"Front Immunol"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01449","article-title":"Effects of IL-34 on macrophage immunological profile in response to Alzheimer's-related A\u03b242 assemblies","volume":"11","author":"Zuroff","year":"2020","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1898176\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:22:33Z","timestamp":1787217753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1898176\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":141,"alternative-id":["10.3389\/fimmu.2026.1898176"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1898176","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]},"article-number":"1898176"}}