{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:45:46Z","timestamp":1791521146630,"version":"4.3.4"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Austrian Science Fund","award":["P 35417-B"],"award-info":[{"award-number":["P 35417-B"]}]},{"name":"Austrian Science Fund","award":["P 35417-B"],"award-info":[{"award-number":["P 35417-B"]}]},{"name":"Austrian Science Fund","award":["P 35417-B"],"award-info":[{"award-number":["P 35417-B"]}]},{"name":"Austrian Science Fund","award":["P 35417-B"],"award-info":[{"award-number":["P 35417-B"]}]},{"name":"Austrian Science Fund","award":["P 35417-B"],"award-info":[{"award-number":["P 35417-B"]}]},{"name":"PMU Research Fund (PMU-FFF) Stand-Alone-Project","award":["E-20\/32\/169-UNG"],"award-info":[{"award-number":["E-20\/32\/169-UNG"]}]},{"name":"PMU Research Fund (PMU-FFF) Stand-Alone-Project","award":["E-20\/32\/169-UNG"],"award-info":[{"award-number":["E-20\/32\/169-UNG"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer\u2019s disease (AD) progression has been associated with the presence of brain-resident CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and recent studies suggest a potential role of the CXCL16-CXCR6 axis in their recruitment to the brain. Here, we examined publicly available single-cell RNA sequencing datasets revealing that in the mouse brain, the receptor\n                    <jats:italic>Cxcr6<\/jats:italic>\n                    is mainly expressed by CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, while the expression of its ligand\n                    <jats:italic>Cxcl16<\/jats:italic>\n                    is predominantly observed in microglial cells. We found higher levels of\n                    <jats:italic>Cxcl16<\/jats:italic>\n                    and\n                    <jats:italic>Cxcr6<\/jats:italic>\n                    expression in APP\/PS1 compared to wild-type mice. Furthermore,\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments using immortalized and primary murine cells suggested that Cxcl16 expression is driven by A\u03b2 pathology. In contrast to our expectations, no changes in the number of Cxcr6\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    cells was evident in the brains of microglia-depleted APP\/PS1 mice, treated with the CSF1R antagonist PLX5622. This was related to an increased compensatory Cxcl16 expression by depletion-resistant microglia or by other brain-resident myeloid cells. Although we demonstrated a strong association between microglial Cxcl16 and AD pathology, PLX5622-sensitive microglia are dispensable in the recruitment of Cxcr6\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells to the brain of APP\/PS1 mice. Future\n                    <jats:italic>in vivo<\/jats:italic>\n                    analysis will help to dissect the mechanism of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell recruitment to the brain.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-22137-5","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T12:41:48Z","timestamp":1761914508000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The involvement of microglia and the CXCL16-CXCR6 axis in the recruitment of CD8+ T cells to an amyloidogenic mouse brain"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8517-2439","authenticated-orcid":false,"given":"Marco","family":"Zattoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0164-2537","authenticated-orcid":false,"given":"Sabine","family":"Bernegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1066-1762","authenticated-orcid":false,"given":"Sofia","family":"Weinbender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-5206","authenticated-orcid":false,"given":"Barbara","family":"Altendorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8373-6813","authenticated-orcid":false,"given":"Heike","family":"Mrowetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6855-6507","authenticated-orcid":false,"given":"Ariane","family":"Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5195-5155","authenticated-orcid":false,"given":"Rodolphe","family":"Poupardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8677-0983","authenticated-orcid":false,"given":"Michael Stefan","family":"Unger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-8046","authenticated-orcid":false,"given":"Ludwig","family":"Aigner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"issue":"7465","key":"22137_CR1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nature12481","volume":"501","author":"M Jucker","year":"2013","unstructured":"Jucker, M. & Walker, L. C. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501 (7465), 45\u201351 (2013).","journal-title":"Nature"},{"issue":"1","key":"22137_CR2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","volume":"14","author":"MA DeTure","year":"2019","unstructured":"DeTure, M. A. & Dickson, D. W. The neuropathological diagnosis of alzheimer\u2019s disease. Mol. Neurodegener. 14 (1), 32 (2019).","journal-title":"Mol. Neurodegener"},{"issue":"4","key":"22137_CR3","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","volume":"14","author":"MT Heneka","year":"2015","unstructured":"Heneka, M. T. et al. Neuroinflammation in alzheimer\u2019s disease. Lancet Neurol. 14 (4), 388\u2013405 (2015).","journal-title":"Lancet Neurol."},{"issue":"1","key":"22137_CR4","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13195-017-0241-2","volume":"9","author":"RM McManus","year":"2017","unstructured":"McManus, R. M. & Heneka, M. T. Role of neuroinflammation in neurodegeneration: new insights. Alzheimers Res. Ther. 9 (1), 14 (2017).","journal-title":"Alzheimers Res. Ther."},{"issue":"3","key":"22137_CR5","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","volume":"17","author":"F Leng","year":"2021","unstructured":"Leng, F. & Edison, P. Neuroinflammation and microglial activation in alzheimer disease: where do we go from here? Nat. Rev. Neurol. 17 (3), 157\u2013172 (2021).","journal-title":"Nat. Rev. Neurol."},{"key":"22137_CR6","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.bbi.2020.05.070","volume":"89","author":"MS Unger","year":"2020","unstructured":"Unger, M. S. et al. CD8\u2009+\u2009T-cells infiltrate alzheimer\u2019s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 Transgenic CD8\u2009+\u2009T-cells infiltrate alzheimer\u2019s disease brains and regulate neuronal- and synapse-related gene expression in APP-PS1 Transgenic mice. Brain Behav. Immun. 89, 67\u201386 (2020).","journal-title":"Brain Behav. Immun."},{"issue":"7790","key":"22137_CR7","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41586-019-1895-7","volume":"577","author":"D Gate","year":"2020","unstructured":"Gate, D. et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in alzheimer\u2019s disease. Nature 577 (7790), 399\u2013404 (2020).","journal-title":"Nature"},{"issue":"1\u20132","key":"22137_CR8","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/S0165-5728(01)00496-9","volume":"124","author":"T Togo","year":"2002","unstructured":"Togo, T. et al. Occurrence of T cells in the brain of alzheimer\u2019s disease and other neurological diseases. J. Neuroimmunol. 124 (1\u20132), 83\u201392 (2002).","journal-title":"J. Neuroimmunol."},{"issue":"4","key":"22137_CR9","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/S0197-4580(88)80079-4","volume":"9","author":"J Rogers","year":"1988","unstructured":"Rogers, J. et al. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of alzheimer\u2019s disease. Neurobiol. Aging. 9 (4), 339\u2013349 (1988).","journal-title":"Neurobiol. Aging"},{"issue":"1","key":"22137_CR10","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1159\/000486200","volume":"18","author":"M Merlini","year":"2018","unstructured":"Merlini, M. et al. Extravascular CD3\u2009+\u2009T cells in brains of alzheimer disease patients correlate with Tau but not with amyloid pathology: an immunohistochemical study. Neurodegener Dis. 18 (1), 49\u201356 (2018).","journal-title":"Neurodegener Dis."},{"issue":"3","key":"22137_CR11","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/0304-3940(88)90690-8","volume":"91","author":"S Itagaki","year":"1988","unstructured":"Itagaki, S., McGeer, P. L. & Akiyama, H. Presence of T-cytotoxic suppressor and leucocyte common antigen positive cells in alzheimer\u2019s disease brain tissue. Neurosci. Lett. 91 (3), 259\u2013264 (1988).","journal-title":"Neurosci. Lett."},{"issue":"1","key":"22137_CR12","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1186\/s12974-018-1304-4","volume":"15","author":"MS Unger","year":"2018","unstructured":"Unger, M. S. et al. Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 Transgenic mice. J. Neuroinflammation. 15 (1), 274 (2018).","journal-title":"J. Neuroinflammation"},{"issue":"4","key":"22137_CR13","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/79738","volume":"1","author":"M Matloubian","year":"2000","unstructured":"Matloubian, M. et al. A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat. Immunol. 1 (4), 298\u2013304 (2000).","journal-title":"Nat. Immunol."},{"issue":"8","key":"22137_CR14","doi-asserted-by":"publisher","first-page":"5145","DOI":"10.4049\/jimmunol.166.8.5145","volume":"166","author":"A Wilbanks","year":"2001","unstructured":"Wilbanks, A. et al. Expression cloning of the STRL33\/BONZO\/TYMSTRligand reveals elements of CC, CXC, and CX3C chemokines. J. Immunol. 166 (8), 5145\u20135154 (2001).","journal-title":"J. Immunol."},{"issue":"3","key":"22137_CR15","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.4049\/jimmunol.170.3.1136","volume":"170","author":"T Nakayama","year":"2003","unstructured":"Nakayama, T. et al. Cutting edge: profile of chemokine receptor expression on human plasma cells accounts for their efficient recruitment to target tissues. J. Immunol. 170 (3), 1136\u20131140 (2003).","journal-title":"J. Immunol."},{"issue":"2","key":"22137_CR16","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1189\/jlb.1003465","volume":"75","author":"T Shimaoka","year":"2004","unstructured":"Shimaoka, T. et al. Cell surface-anchored SR-PSOX\/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells. J. Leukoc. Biol. 75 (2), 267\u2013274 (2004).","journal-title":"J. Leukoc. Biol."},{"key":"22137_CR17","doi-asserted-by":"publisher","first-page":"1022136","DOI":"10.3389\/fimmu.2022.1022136","volume":"13","author":"N Mabrouk","year":"2022","unstructured":"Mabrouk, N. et al. CXCR6 expressing T cells: functions and role in the control of tumors. Front. Immunol. 13, 1022136 (2022).","journal-title":"Front. Immunol."},{"issue":"26","key":"22137_CR18","doi-asserted-by":"publisher","first-page":"5028","DOI":"10.1016\/j.cell.2022.11.019","volume":"185","author":"N Piehl","year":"2022","unstructured":"Piehl, N. et al. Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment. Cell 185 (26), 5028\u20135039e13 (2022).","journal-title":"Cell"},{"issue":"1","key":"22137_CR19","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13073-022-01111-0","volume":"14","author":"SF Rosen","year":"2022","unstructured":"Rosen, S. F. et al. Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16\/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination. Genome Med. 14 (1), 108 (2022).","journal-title":"Genome Med."},{"issue":"7","key":"22137_CR20","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.4049\/jimmunol.2100737","volume":"209","author":"B Altendorfer","year":"2022","unstructured":"Altendorfer, B. et al. Transcriptomic profiling identifies CD8\u2009+\u2009T cells in the brain of aged and alzheimer\u2019s disease Transgenic mice as Tissue-Resident memory T cells. J. Immunol. 209 (7), 1272\u20131285 (2022).","journal-title":"J. Immunol."},{"issue":"6","key":"22137_CR21","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1038\/s41593-019-0393-4","volume":"22","author":"H Van Hove","year":"2019","unstructured":"Van Hove, H. et al. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nat. Neurosci. 22 (6), 1021\u20131035 (2019).","journal-title":"Nat. Neurosci."},{"issue":"1","key":"22137_CR22","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1038\/s41467-022-28803-w","volume":"13","author":"A Ianevski","year":"2022","unstructured":"Ianevski, A., Giri, A. K. & Aittokallio, T. Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data. Nat. Commun. 13 (1), 1246 (2022).","journal-title":"Nat. Commun."},{"issue":"3","key":"22137_CR23","doi-asserted-by":"publisher","first-page":"e10606","DOI":"10.15252\/emmm.201910606","volume":"12","author":"A Sierksma","year":"2020","unstructured":"Sierksma, A. et al. Novel alzheimer risk genes determine the microglia response to amyloid-\u03b2 but not to TAU pathology. EMBO Mol. Med. 12 (3), e10606 (2020).","journal-title":"EMBO Mol. Med."},{"issue":"1","key":"22137_CR24","doi-asserted-by":"publisher","first-page":"3758","DOI":"10.1038\/s41467-019-11674-z","volume":"10","author":"E Spangenberg","year":"2019","unstructured":"Spangenberg, E. et al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an alzheimer\u2019s disease model. Nat. Commun. 10 (1), 3758 (2019).","journal-title":"Nat. Commun."},{"key":"22137_CR25","doi-asserted-by":"publisher","first-page":"e51796","DOI":"10.7554\/eLife.51796","volume":"9","author":"L Zhan","year":"2020","unstructured":"Zhan, L. et al. A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain. Elife 9, e51796 (2020).","journal-title":"Elife"},{"issue":"16","key":"22137_CR26","doi-asserted-by":"publisher","first-page":"2732","DOI":"10.1016\/j.neuron.2024.05.018","volume":"112","author":"DAD Munro","year":"2024","unstructured":"Munro, D. A. D. et al. Microglia protect against age-associated brain pathologies. Neuron 112 (16), 2732\u20132748e8 (2024).","journal-title":"Neuron"},{"issue":"1","key":"22137_CR27","doi-asserted-by":"publisher","first-page":"3215","DOI":"10.1038\/s41467-019-11053-8","volume":"10","author":"R Rojo","year":"2019","unstructured":"Rojo, R. et al. Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations. Nat. Commun. 10 (1), 3215 (2019).","journal-title":"Nat. Commun."},{"issue":"23","key":"22137_CR28","doi-asserted-by":"publisher","first-page":"dev194449","DOI":"10.1242\/dev.194449","volume":"147","author":"DAD Munro","year":"2020","unstructured":"Munro, D. A. D. et al. CNS macrophages differentially rely on an intronic. Development 147(23), dev194449 (2020).","journal-title":"Development"},{"issue":"1","key":"22137_CR29","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13073-025-01498-6","volume":"17","author":"IN Lu","year":"2025","unstructured":"Lu, I. N. et al. The CXCL16\/CXCR6 axis is linked to immune effector cell-associated neurotoxicity in chimeric antigen receptor (CAR) T cell therapy. Genome Med. 17 (1), 71 (2025).","journal-title":"Genome Med."},{"key":"22137_CR30","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1146\/annurev-immunol-042617-053119","volume":"37","author":"PB Narasimhan","year":"2019","unstructured":"Narasimhan, P. B. et al. Nonclassical monocytes in health and disease. Annu. Rev. Immunol. 37, 439\u2013456 (2019).","journal-title":"Annu. Rev. Immunol."},{"issue":"12","key":"22137_CR31","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.1084\/jem.20181308","volume":"216","author":"AN Wein","year":"2019","unstructured":"Wein, A. N. et al. CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways. J. Exp. Med. 216 (12), 2748\u20132762 (2019).","journal-title":"J. Exp. Med."},{"issue":"9","key":"22137_CR32","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1086\/656532","volume":"202","author":"B Woehrl","year":"2010","unstructured":"Woehrl, B. et al. CXCL16 contributes to neutrophil recruitment to cerebrospinal fluid in Pneumococcal meningitis. J. Infect. Dis. 202 (9), 1389\u20131396 (2010).","journal-title":"J. Infect. Dis."},{"issue":"7","key":"22137_CR33","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.3390\/ijms18071468","volume":"18","author":"V Adamski","year":"2017","unstructured":"Adamski, V. et al. The chemokine receptor CXCR6 evokes reverse signaling via the transmembrane chemokine CXCL16. Int. J. Mol. Sci. 18(7), 1468 (2017).","journal-title":"Int. J. Mol. Sci."},{"issue":"1\u20132","key":"22137_CR34","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jneuroim.2013.04.006","volume":"260","author":"K Hattermann","year":"2013","unstructured":"Hattermann, K. et al. The CXCL16-CXCR6 chemokine axis in glial tumors. J. Neuroimmunol. 260 (1\u20132), 47\u201354 (2013).","journal-title":"J. Neuroimmunol."},{"key":"22137_CR35","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41523-017-0008-8","volume":"3","author":"B Chung","year":"2017","unstructured":"Chung, B. et al. Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12. NPJ Breast Cancer. 3, 6 (2017).","journal-title":"NPJ Breast Cancer"},{"issue":"1","key":"22137_CR36","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13195-022-01159-5","volume":"15","author":"X Li","year":"2023","unstructured":"Li, X. et al. Convergent transcriptomic and genomic evidence supporting a dysregulation of CXCL16 and CCL5 in alzheimer\u2019s disease. Alzheimers Res. Ther. 15 (1), 17 (2023).","journal-title":"Alzheimers Res. Ther."},{"issue":"9","key":"22137_CR37","doi-asserted-by":"publisher","first-page":"e0274350","DOI":"10.1371\/journal.pone.0274350","volume":"17","author":"Y Fang","year":"2022","unstructured":"Fang, Y. et al. Association between inflammatory biomarkers and cognitive aging. PLoS One. 17 (9), e0274350 (2022).","journal-title":"PLoS One"},{"issue":"17","key":"22137_CR38","first-page":"3911","volume":"21","author":"G Jin","year":"2017","unstructured":"Jin, G. The relationship between serum CXCL16 level and carotid vulnerable plaque in patients with ischemic stroke. Eur. Rev. Med. Pharmacol. Sci. 21 (17), 3911\u20133915 (2017).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"22137_CR39","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.3389\/fimmu.2019.02337","volume":"10","author":"S Romero-Su\u00e1rez","year":"2019","unstructured":"Romero-Su\u00e1rez, S. et al. The central nervous system contains ILC1s that differ from NK cells in the response to inflammation. Front. Immunol. 10, 2337 (2019).","journal-title":"Front. Immunol."},{"key":"22137_CR40","doi-asserted-by":"publisher","first-page":"p590409","DOI":"10.1155\/2014\/590409","volume":"2014","author":"DW Wojkowska","year":"2014","unstructured":"Wojkowska, D. W. et al. Interactions between neutrophils, Th17 cells, and chemokines during the initiation of experimental model of multiple sclerosis. Mediators Inflamm. 2014, p590409 (2014).","journal-title":"Mediators Inflamm."},{"issue":"1\u20132","key":"22137_CR41","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.neulet.2005.12.029","volume":"397","author":"LM le Blanc","year":"2006","unstructured":"le Blanc, L. M. et al. CXCL16 is elevated in the cerebrospinal fluid versus serum and in inflammatory conditions with suspected and proved central nervous system involvement. Neurosci. Lett. 397 (1\u20132), 145\u2013148 (2006).","journal-title":"Neurosci. Lett."},{"key":"22137_CR42","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3389\/fncel.2014.00193","volume":"8","author":"M Rosito","year":"2014","unstructured":"Rosito, M. et al. Trasmembrane chemokines CX3CL1 and CXCL16 drive interplay between neurons, microglia and astrocytes to counteract pMCAO and excitotoxic neuronal death. Front. Cell. Neurosci. 8, 193 (2014).","journal-title":"Front. Cell. Neurosci."},{"key":"22137_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1742-2094-6-1","volume":"6","author":"CM Sondag","year":"2009","unstructured":"Sondag, C. M., Dhawan, G. & Combs, C. K. Beta amyloid oligomers and fibrils stimulate differential activation of primary microglia. J. Neuroinflammation. 6, 1 (2009).","journal-title":"J. Neuroinflammation"},{"issue":"Pt A","key":"22137_CR44","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.brainres.2016.08.016","volume":"1648","author":"LK Gouwens","year":"2016","unstructured":"Gouwens, L. K. et al. Amyloid-\u03b242 protofibrils are internalized by microglia more extensively than monomers. Brain Res. 1648 (Pt A), 485\u2013495 (2016).","journal-title":"Brain Res."},{"issue":"6","key":"22137_CR45","doi-asserted-by":"publisher","first-page":"3678","DOI":"10.4049\/jimmunol.172.6.3678","volume":"172","author":"PJ Gough","year":"2004","unstructured":"Gough, P. J. et al. A disintegrin and metalloproteinase 10-mediated cleavage and shedding regulates the cell surface expression of CXC chemokine ligand 16. J. Immunol. 172 (6), 3678\u20133685 (2004).","journal-title":"J. Immunol."},{"issue":"5","key":"22137_CR46","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1111\/j.1471-4159.2005.03123.x","volume":"93","author":"A Ludwig","year":"2005","unstructured":"Ludwig, A. et al. Enhanced expression and shedding of the transmembrane chemokine CXCL16 by reactive astrocytes and glioma cells. J. Neurochem. 93 (5), 1293\u20131303 (2005).","journal-title":"J. Neurochem"},{"issue":"6","key":"22137_CR47","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1093\/brain\/awaa117","volume":"143","author":"NL Fransen","year":"2020","unstructured":"Fransen, N. L. et al. Tissue-resident memory T cells invade the brain parenchyma in multiple sclerosis white matter lesions. Brain 143 (6), 1714\u20131730 (2020).","journal-title":"Brain"},{"issue":"2","key":"22137_CR48","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1002\/eji.202048665","volume":"51","author":"CC Hsiao","year":"2021","unstructured":"Hsiao, C. C. et al. White matter lesions in multiple sclerosis are enriched for CD20. Eur. J. Immunol. 51 (2), 483\u2013486 (2021).","journal-title":"Eur. J. Immunol."},{"key":"22137_CR49","doi-asserted-by":"publisher","first-page":"850226","DOI":"10.3389\/fimmu.2022.850226","volume":"13","author":"PM Kollis","year":"2022","unstructured":"Kollis, P. M. et al. Characterising distinct migratory profiles of infiltrating T-Cell subsets in human glioblastoma. Front. Immunol. 13, 850226 (2022).","journal-title":"Front. Immunol."},{"issue":"1","key":"22137_CR50","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1186\/s12974-022-02611-x","volume":"19","author":"PA Unger","year":"2022","unstructured":"Unger, P. A. et al. T-cells in human trigeminal ganglia express canonical tissue-resident memory T-cell markers. J. Neuroinflammation. 19 (1), 249 (2022).","journal-title":"J. Neuroinflammation"},{"issue":"7953","key":"22137_CR51","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41586-023-05788-0","volume":"615","author":"X Chen","year":"2023","unstructured":"Chen, X. et al. Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy. Nature 615 (7953), 668\u2013677 (2023).","journal-title":"Nature"},{"issue":"11","key":"22137_CR52","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1002\/glia.23844","volume":"68","author":"V Mangale","year":"2020","unstructured":"Mangale, V. et al. Microglia influence host defense, disease, and repair following murine coronavirus infection of the central nervous system. Glia 68 (11), 2345\u20132360 (2020).","journal-title":"Glia"},{"key":"22137_CR53","doi-asserted-by":"publisher","first-page":"851556","DOI":"10.3389\/fimmu.2022.851556","volume":"13","author":"AG Spiteri","year":"2022","unstructured":"Spiteri, A. G. et al. PLX5622 reduces disease severity in lethal CNS infection by Off-Target Inhibition of peripheral inflammatory monocyte production. Front. Immunol. 13, 851556 (2022).","journal-title":"Front. Immunol."},{"issue":"1","key":"22137_CR54","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41514-024-00145-5","volume":"10","author":"MR Costa","year":"2024","unstructured":"Costa, M. R. Switch of innate to adaptative immune responses in the brain of patients with alzheimer\u2019s disease correlates with tauopathy progression. NPJ Aging. 10 (1), 19 (2024).","journal-title":"NPJ Aging"},{"key":"22137_CR55","doi-asserted-by":"publisher","first-page":"34633","DOI":"10.1038\/srep34633","volume":"6","author":"MA Di Castro","year":"2016","unstructured":"Di Castro, M. A. et al. The chemokine CXCL16 modulates neurotransmitter release in hippocampal CA1 area. Sci. Rep. 6, 34633 (2016).","journal-title":"Sci. Rep."},{"key":"22137_CR56","doi-asserted-by":"publisher","first-page":"2750","DOI":"10.3389\/fimmu.2018.02750","volume":"9","author":"F Lepore","year":"2018","unstructured":"Lepore, F. et al. CXCL16\/CXCR6 axis drives Microglia\/Macrophages phenotype in physiological conditions and plays a crucial role in glioma. Front. Immunol. 9, 2750 (2018).","journal-title":"Front. Immunol."},{"issue":"10","key":"22137_CR57","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1038\/s41590-023-01604-z","volume":"24","author":"W Su","year":"2023","unstructured":"Su, W. et al. CXCR6 orchestrates brain CD8+ T cell residency and limits mouse alzheimer\u2019s disease pathology. Nat. Immunol. 24 (10), 1735\u20131747 (2023).","journal-title":"Nat. Immunol."},{"key":"22137_CR58","doi-asserted-by":"crossref","unstructured":"Sharon, A., Erez, H. & Spira, M. E. Significant Sex Differences in the Efficacy of the CSF1R Inhibitor-PLX5622 on Rat Brain Microglia Elimination\u00a015, Pharmaceuticals, Basel, (2022).","DOI":"10.3390\/ph15050569"},{"issue":"1","key":"22137_CR59","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/s41467-022-35753-w","volume":"14","author":"NR Johnson","year":"2023","unstructured":"Johnson, N. R. et al. CSF1R inhibitors induce a sex-specific resilient microglial phenotype and functional rescue in a tauopathy mouse model. Nat. Commun. 14 (1), 118 (2023).","journal-title":"Nat. Commun."},{"issue":"38","key":"22137_CR60","doi-asserted-by":"publisher","first-page":"23336","DOI":"10.1073\/pnas.1922788117","volume":"117","author":"F Lei","year":"2020","unstructured":"Lei, F. et al. CSF1R Inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages. Proc. Natl. Acad. Sci. U S A. 117 (38), 23336\u201323338 (2020).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"22137_CR61","doi-asserted-by":"publisher","first-page":"621090","DOI":"10.3389\/fimmu.2021.621090","volume":"12","author":"JMS Sanchez","year":"2021","unstructured":"Sanchez, J. M. S. et al. The CSF1R-Microglia axis has protective Host-Specific roles during neurotropic picornavirus infection. Front. Immunol. 12, 621090 (2021).","journal-title":"Front. Immunol."},{"issue":"3","key":"22137_CR62","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1172\/JCI97229","volume":"128","author":"DL Wheeler","year":"2018","unstructured":"Wheeler, D. L. et al. Microglia are required for protection against lethal coronavirus encephalitis in mice. J. Clin. Invest. 128 (3), 931\u2013943 (2018).","journal-title":"J. Clin. Invest."},{"issue":"1","key":"22137_CR63","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41419-023-05551-3","volume":"14","author":"A Montilla","year":"2023","unstructured":"Montilla, A. et al. Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis. Cell. Death Dis. 14 (1), 16 (2023).","journal-title":"Cell. Death Dis."},{"issue":"6","key":"22137_CR64","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1038\/s41593-025-01955-w","volume":"28","author":"J Groh","year":"2025","unstructured":"Groh, J. et al. Microglia activation orchestrates CXCL10-mediated CD8. Nat. Neurosci. 28 (6), 1160\u20131173 (2025).","journal-title":"Nat. Neurosci."},{"issue":"6594","key":"22137_CR65","doi-asserted-by":"publisher","first-page":"eabd5926","DOI":"10.1126\/science.abd5926","volume":"376","author":"L Zhou","year":"2022","unstructured":"Zhou, L. et al. Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline. Science 376 (6594), eabd5926 (2022).","journal-title":"Science"},{"issue":"17","key":"22137_CR66","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.3390\/cells11172649","volume":"11","author":"C Harrer","year":"2022","unstructured":"Harrer, C. et al. The CXCL13\/CXCR5 immune axis in health and disease-implications for intrathecal B cell activities in neuroinflammation. Cells 11(17), 2649 (2022).","journal-title":"Cells"},{"issue":"1","key":"22137_CR67","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12987-021-00272-1","volume":"18","author":"C Harrer","year":"2021","unstructured":"Harrer, C. et al. The CXCL13\/CXCR5-chemokine axis in neuroinflammation: evidence of CXCR5\u2009+\u2009CD4 T cell recruitment to CSF. Fluids Barriers CNS. 18 (1), 40 (2021).","journal-title":"Fluids Barriers CNS"},{"issue":"9","key":"22137_CR68","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1038\/s41593-023-01415-3","volume":"26","author":"M Jorfi","year":"2023","unstructured":"Jorfi, M. et al. Infiltrating CD8+ T cells exacerbate alzheimer\u2019s disease pathology in a 3D human neuroimmune axis model. Nat. Neurosci. 26 (9), 1489\u20131504 (2023).","journal-title":"Nat. Neurosci."},{"key":"22137_CR69","first-page":"e090394","volume":"20","author":"R Mancuso","year":"2024","unstructured":"Mancuso, R. et al. Xenografted human microglia display diverse transcriptomic states in response to Alzheimer\u2019s disease-related amyloid-\u03b2 pathology. Nat. Neurosci. 20, e090394 (2024).","journal-title":"Nat. Neurosci."},{"issue":"4","key":"22137_CR70","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1016\/j.celrep.2019.03.099","volume":"27","author":"C Sala Frigerio","year":"2019","unstructured":"Sala Frigerio, C. et al. The major risk factors for alzheimer\u2019s disease: Age, Sex, and genes modulate the microglia response to A\u03b2 plaques. Cell. Rep. 27 (4), 1293\u20131306e6 (2019).","journal-title":"Cell. Rep."},{"issue":"9","key":"22137_CR71","doi-asserted-by":"publisher","first-page":"e20202717","DOI":"10.1084\/jem.20202717","volume":"218","author":"Y Chen","year":"2021","unstructured":"Chen, Y. & Colonna, M. Microglia in Alzheimer\u2019s disease at single-cell level. are there common patterns in humans and mice?. J. Exp. Med. 218(9), e20202717 (2021).","journal-title":"J. Exp. Med."},{"key":"22137_CR72","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.brainresrev.2004.12.003","volume":"48","author":"K F\u00e4rber","year":"2005","unstructured":"F\u00e4rber, K. & Kettenmann, H. Physiology of microglial cells. Brain Res. Rev. 48, 133\u2013143 (2005).","journal-title":"Brain Res. Rev."},{"issue":"11","key":"22137_CR73","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.4049\/jimmunol.137.11.3521","volume":"137","author":"K Frei","year":"1986","unstructured":"Frei, K. et al. Astrocyte-derived Interleukin 3 as a growth factor for microglia cells and peritoneal macrophages. J. Immunol. 137 (11), 3521\u20133527 (1986).","journal-title":"J. Immunol."},{"issue":"8","key":"22137_CR74","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1523\/JNEUROSCI.06-08-02163.1986","volume":"6","author":"D Giulian","year":"1986","unstructured":"Giulian, D. & Baker, T. J. Characterization of ameboid microglia isolated from developing mammalian brain. J. Neurosci. 6 (8), 2163\u20132178 (1986).","journal-title":"J. Neurosci."},{"issue":"10","key":"22137_CR75","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1097\/00005072-199910000-00006","volume":"58","author":"M Prinz","year":"1999","unstructured":"Prinz, M. et al. Microglial activation by components of gram-positive and -negative bacteria: distinct and common routes to the induction of ion channels and cytokines. J. Neuropathol. Exp. Neurol. 58 (10), 1078\u20131089 (1999).","journal-title":"J. Neuropathol. Exp. Neurol."},{"issue":"11","key":"22137_CR76","doi-asserted-by":"publisher","first-page":"5752","DOI":"10.4049\/jimmunol.1103426","volume":"188","author":"DC Lacey","year":"2012","unstructured":"Lacey, D. C. et al. Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models. J. Immunol. 188 (11), 5752\u20135765 (2012).","journal-title":"J. Immunol."},{"issue":"1","key":"22137_CR77","doi-asserted-by":"publisher","first-page":"100246","DOI":"10.1016\/j.xpro.2020.100246","volume":"2","author":"G Toda","year":"2021","unstructured":"Toda, G. et al. Preparation and culture of bone marrow-derived macrophages from mice for functional analysis. STAR. Protoc. 2 (1), 100246 (2021).","journal-title":"STAR. Protoc."},{"issue":"4","key":"22137_CR78","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta delta C(T)) method. Methods 25 (4), 402\u2013408 (2001).","journal-title":"Methods"}],"updated-by":[{"DOI":"10.1038\/s41598-026-51926-9","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22137-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22137-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22137-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:03:42Z","timestamp":1782309822000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22137-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["22137"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-22137-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]},"assertion":[{"value":"15 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-026-51926-9","URL":"https:\/\/doi.org\/10.1038\/s41598-026-51926-9","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All animal experiments were conducted in compliance with national ethical guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"All animal experiments were approved by the Austrian Ministry of Science and Research (BMBFW-66.019\/0011-WF\/V\/3b\/2016 and BMBFW: 2020\u2009\u2212\u20090.827.682) and were performed in accordance with relevant named guidelines and regulations. Furthermore, the authors complied with the ARRIVE guidelines, as the \u201cARRIVE 10 essentials\u201d are described in details in the \u201cMethods\u201d section.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Approval for animal experiments"}}],"article-number":"38221"}}