{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:37:34Z","timestamp":1793284654938,"version":"4.5.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007051","name":"Uppsala University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lipid droplets (LDs) are crucial for energy homeostasis, but are also involved in a wide spectrum of other cellular processes. Accumulating data identifies LDs as an important player in inflammation. However, the underlying mechanisms and the impact of LDs on neuroinflammation remain unclear. Here, we describe a novel function of LDs in human astrocytes, in the context of Alzheimer\u2019s disease (AD). Although, the overall lipid profile was unchanged in astrocytes with AD pathology, our data show a clear effect on LD metabolism and specific fatty acids involved in neuroinflammation. Importantly, we found astrocytes to be in close contact with infiltrating CD4\u2009+\u2009T cells in the AD brain. Moreover, PLIN3\u2009+\u2009LDs in astrocytes co-localize with major histocompatibility complex II (MHCII), indicating a role of LDs in adaptive immunity. Comprehensive analysis of human induced pluripotent stem cell (hiPSC)-derived astrocytes revealed that MHCII is in fact loaded within PLIN3\u2009+\u2009LDs and forwarded to neighboring cells via tunneling nanotubes and secretion. Notably, the MHCII molecules are cleaved into its active form prior to packing, indicating an alternative route of MHCII shuttling through LDs, transporting functional immune complexes between cells. Quantification of PLIN3\u2009+\u2009LDs in astrocytic cultures, human brain tissue and cerebral organoids indicates that AD pathology initially stimulates PLIN3\u2009+\u2009LD formation, but in the long-run results in PLIN3\u2009+\u2009LD consumption, which may have consequences on the astrocytes\u2019 MHCII distribution capacity. Taken together, our findings present a novel function of PLIN3\u2009+\u2009LDs that can be of relevance for AD and other inflammatory conditions.<\/jats:p>","DOI":"10.1186\/s12974-025-03452-0","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T11:29:20Z","timestamp":1745494160000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Astrocytic lipid droplets contain MHCII and may act as cogs in the antigen presentation machinery"],"prefix":"10.1186","volume":"22","author":[{"given":"Chiara","family":"Beretta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulkhalek","family":"Dakhel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Eltom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Rosqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Uzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Mothes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Ris\u00e9rus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag","family":"Sehlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinar","family":"Rostami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech Piotr","family":"Michno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Erlandsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"3452_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","volume":"119","author":"MV Sofroniew","year":"2010","unstructured":"Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119:7\u201335.","journal-title":"Acta Neuropathol"},{"key":"3452_CR2","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1016\/j.cell.2019.04.001","volume":"177","author":"MS Ioannou","year":"2019","unstructured":"Ioannou MS, et al. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell. 2019;177:1522\u2013e153514.","journal-title":"Cell"},{"key":"3452_CR3","doi-asserted-by":"crossref","unstructured":"Barber CN, Raben DM. Lipid metabolism crosstalk in the brain: glia and neurons. Front Cell Neurosci. 2019;13.","DOI":"10.3389\/fncel.2019.00212"},{"key":"3452_CR4","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.15252\/embr.201439225","volume":"15","author":"MG Mart\u00edn","year":"2014","unstructured":"Mart\u00edn MG, Pfrieger F, Dotti CG. Cholesterol in brain disease: sometimes determinant and frequently implicated. EMBO Rep. 2014;15:1036\u201352.","journal-title":"EMBO Rep"},{"key":"3452_CR5","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1053\/j.gastro.2012.06.003","volume":"143","author":"J Ibrahim","year":"2012","unstructured":"Ibrahim J, et al. Dendritic cell populations with different concentrations of lipid regulate tolerance and immunity in mouse and human liver. Gastroenterology. 2012;143:1061\u201372.","journal-title":"Gastroenterology"},{"key":"3452_CR6","doi-asserted-by":"publisher","unstructured":"Gandotra S. Chapter 10 - Lipid droplets in the immune response and beyond. in Lipid Signaling and Metabolism (ed. Ntambi, J. M.) 173\u2013196 Academic Press. 2020. https:\/\/doi.org\/10.1016\/B978-0-12-819404-1.00010-5","DOI":"10.1016\/B978-0-12-819404-1.00010-5"},{"key":"3452_CR7","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1038\/s41467-017-02186-9","volume":"8","author":"F Veglia","year":"2017","unstructured":"Veglia F, et al. Lipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer. Nat Commun. 2017;8:2122.","journal-title":"Nat Commun"},{"key":"3452_CR8","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.immuni.2009.06.022","volume":"31","author":"L Bougn\u00e8res","year":"2009","unstructured":"Bougn\u00e8res L, et al. A role for lipid bodies in the cross-presentation of phagocytosed antigens by MHC class I in dendritic cells. Immunity. 2009;31:232\u201344.","journal-title":"Immunity"},{"key":"3452_CR9","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/nri3859","volume":"15","author":"EA Dennis","year":"2015","unstructured":"Dennis EA, Norris PC. Eicosanoid storm in infection and inflammation. Nat Rev Immunol. 2015;15:511\u201323.","journal-title":"Nat Rev Immunol"},{"key":"3452_CR10","doi-asserted-by":"publisher","first-page":"eaaz6314","DOI":"10.1126\/scitranslmed.aaz6314","volume":"13","author":"X Liu","year":"2021","unstructured":"Liu X, et al. Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy. Sci Transl Med. 2021;13:eaaz6314.","journal-title":"Sci Transl Med"},{"key":"3452_CR11","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.it.2018.01.012","volume":"39","author":"MH den Brok","year":"2018","unstructured":"den Brok MH, Raaijmakers TK, Collado-Camps E, Adema GJ. Lipid droplets as immune modulators in myeloid cells. Trends Immunol. 2018;39:380\u201392.","journal-title":"Trends Immunol"},{"key":"3452_CR12","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.plefa.2011.04.020","volume":"85","author":"PT Bozza","year":"2011","unstructured":"Bozza PT, Bakker-Abreu I, Navarro-Xavier RA, Bandeira-Melo C. Lipid body function in eicosanoid synthesis: an update. Prostaglandins Leukot Essent Fat Acids. 2011;85:205\u201313.","journal-title":"Prostaglandins Leukot Essent Fat Acids"},{"key":"3452_CR13","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.it.2020.07.004","volume":"41","author":"MV Sofroniew","year":"2020","unstructured":"Sofroniew MV. Astrocyte reactivity: subtypes, states, and functions in CNS innate immunity. Trends Immunol. 2020;41:758\u201370.","journal-title":"Trends Immunol"},{"key":"3452_CR14","doi-asserted-by":"publisher","first-page":"29539","DOI":"10.1038\/srep29539","volume":"6","author":"S Zhang","year":"2016","unstructured":"Zhang S, et al. Morphologically and functionally distinct lipid droplet subpopulations. Sci Rep. 2016;6:29539.","journal-title":"Sci Rep"},{"key":"3452_CR15","doi-asserted-by":"publisher","first-page":"e98947","DOI":"10.15252\/embj.201898947","volume":"37","author":"WM Henne","year":"2018","unstructured":"Henne WM, Reese ML, Goodman JM. The assembly of lipid droplets and their roles in challenged cells. EMBO J. 2018;37:e98947.","journal-title":"EMBO J"},{"key":"3452_CR16","first-page":"419","volume":"1791","author":"PE Bickel","year":"2009","unstructured":"Bickel PE, Tansey JT, Welte MA. PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochim Et Biophys Acta (BBA) - Mol Cell Biology Lipids. 2009;1791:419\u201340.","journal-title":"Biochim Et Biophys Acta (BBA) - Mol Cell Biology Lipids"},{"key":"3452_CR17","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1002\/1873-3468.14792","volume":"598","author":"E Griseti","year":"2024","unstructured":"Griseti E, et al. Molecular mechanisms of perilipin protein function in lipid droplet metabolism. FEBS Lett. 2024;598:1170\u201398.","journal-title":"FEBS Lett"},{"key":"3452_CR18","doi-asserted-by":"publisher","first-page":"e12756","DOI":"10.1111\/nan.12756","volume":"48","author":"M Conte","year":"2022","unstructured":"Conte M, et al. Expression pattern of perilipins in human brain during aging and in Alzheimer\u2019s disease. Neuropathol Appl Neurobiol. 2022;48:e12756.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"3452_CR19","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.4049\/jimmunol.157.5.1819","volume":"157","author":"P Shrikant","year":"1996","unstructured":"Shrikant P, Benveniste EN. The central nervous system as an immunocompetent organ: role of glial cells in antigen presentation. J Immunol. 1996;157:1819\u201322.","journal-title":"J Immunol"},{"key":"3452_CR20","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/1742-2094-9-144","volume":"9","author":"N Vardjan","year":"2012","unstructured":"Vardjan N, et al. IFN-\u03b3-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments. J Neuroinflamm. 2012;9:144.","journal-title":"J Neuroinflamm"},{"key":"3452_CR21","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s12974-020-01776-7","volume":"17","author":"J Rostami","year":"2020","unstructured":"Rostami J, et al. Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson\u2019s disease brain. J Neuroinflamm. 2020;17:119.","journal-title":"J Neuroinflamm"},{"key":"3452_CR22","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1016\/j.stemcr.2018.01.021","volume":"10","author":"A Lundin","year":"2018","unstructured":"Lundin A, et al. Human iPS-derived astroglia from a stable neural precursor state show improved functionality compared with conventional astrocytic models. Stem Cell Rep. 2018;10:1030\u201345.","journal-title":"Stem Cell Rep"},{"key":"3452_CR23","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1111\/j.1471-4159.2007.04759.x","volume":"103","author":"H Englund","year":"2007","unstructured":"Englund H, et al. Sensitive ELISA detection of amyloid-beta protofibrils in biological samples. J Neurochem. 2007;103:334\u201345.","journal-title":"J Neurochem"},{"key":"3452_CR24","doi-asserted-by":"publisher","first-page":"e32014","DOI":"10.1371\/journal.pone.0032014","volume":"7","author":"D Sehlin","year":"2012","unstructured":"Sehlin D, et al. Large aggregates are the major soluble A\u03b2 species in AD brain fractionated with density gradient ultracentrifugation. PLoS ONE. 2012;7:e32014.","journal-title":"PLoS ONE"},{"key":"3452_CR25","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s13024-016-0098-z","volume":"11","author":"S S\u00f6llvander","year":"2016","unstructured":"S\u00f6llvander S, et al. Accumulation of amyloid-\u03b2 by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons. Mol Neurodegeneration. 2016;11:38.","journal-title":"Mol Neurodegeneration"},{"key":"3452_CR26","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1194\/jlr.D700041-JLR200","volume":"49","author":"V Matyash","year":"2008","unstructured":"Matyash V, Liebisch G, Kurzchalia TV, Shevchenko A, Schwudke D. Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J Lipid Res. 2008;49:1137\u201346.","journal-title":"J Lipid Res"},{"key":"3452_CR27","doi-asserted-by":"publisher","first-page":"9058","DOI":"10.1021\/ac8015278","volume":"80","author":"JS Fletcher","year":"2008","unstructured":"Fletcher JS, et al. A new dynamic in mass spectral imaging of single biological cells. Anal Chem. 2008;80:9058\u201364.","journal-title":"Anal Chem"},{"key":"3452_CR28","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1017\/S0007114500002154","volume":"84","author":"GC Burdge","year":"2000","unstructured":"Burdge GC, Wright P, Jones AE, Wootton SA. A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extraction. Br J Nutr. 2000;84:781\u20137.","journal-title":"Br J Nutr"},{"key":"3452_CR29","unstructured":"ChiToolbox\/ChiToolbox\/@ChiMSCharacter\/peakdetect.m at master \u00b7 AlexHenderson\/ChiToolbox. GitHubhttps:\/\/github.com\/AlexHenderson\/ChiToolbox\/blob\/master\/ChiToolbox\/%40ChiMSCharacter\/peakdetect.m"},{"key":"3452_CR30","doi-asserted-by":"publisher","first-page":"D527","DOI":"10.1093\/nar\/gkl838","volume":"35","author":"M Sud","year":"2007","unstructured":"Sud M, et al. LMSD: LIPID MAPS structure database. Nucleic Acids Res. 2007;35:D527\u201332.","journal-title":"Nucleic Acids Res"},{"key":"3452_CR31","doi-asserted-by":"publisher","first-page":"e58","DOI":"10.1002\/cpim.58","volume":"123","author":"MS Alam","year":"2018","unstructured":"Alam MS. Proximity ligation assay (PLA). Curr Protocols Immunol. 2018;123:e58.","journal-title":"Curr Protocols Immunol"},{"key":"3452_CR32","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nri3818","volume":"15","author":"PA Roche","year":"2015","unstructured":"Roche PA, Furuta K. The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol. 2015;15:203\u201316.","journal-title":"Nat Rev Immunol"},{"key":"3452_CR33","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s40478-023-01589-8","volume":"11","author":"T Mothes","year":"2023","unstructured":"Mothes T, et al. Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology. Acta Neuropathol Commun. 2023;11:97.","journal-title":"Acta Neuropathol Commun"},{"key":"3452_CR34","doi-asserted-by":"publisher","first-page":"11835","DOI":"10.1523\/JNEUROSCI.0983-17.2017","volume":"37","author":"J Rostami","year":"2017","unstructured":"Rostami J, et al. Human astrocytes transfer aggregated alpha-synuclein via tunneling nanotubes. J Neurosci. 2017;37:11835\u201353.","journal-title":"J Neurosci"},{"key":"3452_CR35","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12974-023-02722-z","volume":"20","author":"M Zy\u015bk","year":"2023","unstructured":"Zy\u015bk M, et al. Amyloid-\u03b2 accumulation in human astrocytes induces mitochondrial disruption and changed energy metabolism. J Neuroinflamm. 2023;20:43.","journal-title":"J Neuroinflamm"},{"key":"3452_CR36","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","volume":"23","author":"J Marschallinger","year":"2020","unstructured":"Marschallinger J, et al. Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain. Nat Neurosci. 2020;23:194\u2013208.","journal-title":"Nat Neurosci"},{"key":"3452_CR37","doi-asserted-by":"publisher","first-page":"eaaz4564","DOI":"10.1126\/scitranslmed.aaz4564","volume":"13","author":"G Sienski","year":"2021","unstructured":"Sienski G, et al. APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia. Sci Transl Med. 2021;13:eaaz4564.","journal-title":"Sci Transl Med"},{"key":"3452_CR38","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/s41586-022-05439-w","volume":"611","author":"JW Blanchard","year":"2022","unstructured":"Blanchard JW, et al. APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature. 2022;611:769\u201379.","journal-title":"Nature"},{"key":"3452_CR39","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/j.1745-7254.2006.00259.x","volume":"27","author":"Z Wang","year":"2006","unstructured":"Wang Z, Li G, Tang W, Yin M. Neuroprotective effects of stearic acid against toxicity of oxygen\/glucose deprivation or glutamate on rat cortical or hippocampal slices. Acta Pharmacol Sin. 2006;27:145\u201350.","journal-title":"Acta Pharmacol Sin"},{"key":"3452_CR40","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.cbi.2005.12.008","volume":"160","author":"Z-J Wang","year":"2006","unstructured":"Wang Z-J, Li G-M, Nie B-M, Lu Y, Yin M. Neuroprotective effect of the stearic acid against oxidative stress via phosphatidylinositol 3-kinase pathway. Chem Biol Interact. 2006;160:80\u20137.","journal-title":"Chem Biol Interact"},{"key":"3452_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.29245\/2572.942X\/2016\/9.1086","volume":"1","author":"J-L Olivier","year":"2016","unstructured":"Olivier J-L. Arachidonic acid in Alzheimer\u2019s disease. J Neurol Neuromedicine. 2016;1:1\u20136.","journal-title":"J Neurol Neuromedicine"},{"key":"3452_CR42","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.it.2007.01.005","volume":"28","author":"C Farina","year":"2007","unstructured":"Farina C, Aloisi F, Meinl E. Astrocytes are active players in cerebral innate immunity. Trends Immunol. 2007;28:138\u201345.","journal-title":"Trends Immunol"},{"key":"3452_CR43","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","volume":"14","author":"MT Heneka","year":"2015","unstructured":"Heneka MT, et al. Neuroinflammation in Alzheimer\u2019s disease. Lancet Neurol. 2015;14:388\u2013405.","journal-title":"Lancet Neurol"},{"key":"3452_CR44","doi-asserted-by":"publisher","first-page":"824411","DOI":"10.3389\/fimmu.2022.824411","volume":"13","author":"M Kunkl","year":"2022","unstructured":"Kunkl M, Amormino C, Tedeschi V, Fiorillo MT, Tuosto L. Astrocytes and inflammatory T helper cells: a dangerous liaison in multiple sclerosis. Front Immunol. 2022;13:824411.","journal-title":"Front Immunol"},{"key":"3452_CR45","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1159\/000486200","volume":"18","author":"M Merlini","year":"2018","unstructured":"Merlini M, Kirabali T, Kulic L, Nitsch RM, Ferretti MT. Extravascular CD3\u2009+\u2009T cells in brains of alzheimer disease patients correlate with tau but not with amyloid pathology: an immunohistochemical study. Neurodegener Dis. 2018;18:49\u201356.","journal-title":"Neurodegener Dis"},{"key":"3452_CR46","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. 2002;124:83\u201392.","journal-title":"J Neuroimmunol"},{"key":"3452_CR47","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1172\/JCI200318104","volume":"112","author":"A Monsonego","year":"2003","unstructured":"Monsonego A, et al. Increased T cell reactivity to amyloid beta protein in older humans and patients with alzheimer disease. J Clin Invest. 2003;112:415\u201322.","journal-title":"J Clin Invest"},{"key":"3452_CR48","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.stem.2015.08.001","volume":"17","author":"LK Hamilton","year":"2015","unstructured":"Hamilton LK, et al. Aberrant lipid metabolism in the forebrain niche suppresses adult neural stem cell proliferation in an animal model of Alzheimer\u2019s disease. Cell Stem Cell. 2015;17:397\u2013411.","journal-title":"Cell Stem Cell"},{"key":"3452_CR49","doi-asserted-by":"crossref","unstructured":"Zhang Y et al. Astrocyte metabolism and signaling pathways in the CNS. Front Neurosci. 2023;17.","DOI":"10.3389\/fnins.2023.1217451"},{"key":"3452_CR50","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1080\/14789450.2021.1995356","volume":"18","author":"FS Pereira-Dutra","year":"2021","unstructured":"Pereira-Dutra FS, Bozza PT. Lipid droplets diversity and functions in inflammation and immune response. Expert Rev Proteom. 2021;18:809\u201325.","journal-title":"Expert Rev Proteom"},{"key":"3452_CR51","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1038\/nm.3704","volume":"20","author":"L Berod","year":"2014","unstructured":"Berod L, et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med. 2014;20:1327\u201333.","journal-title":"Nat Med"},{"key":"3452_CR52","doi-asserted-by":"publisher","first-page":"3299","DOI":"10.4049\/jimmunol.1003613","volume":"186","author":"RD Michalek","year":"2011","unstructured":"Michalek RD, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4\u2009+\u2009T cell subsets. J Immunol. 2011;186:3299\u2013303.","journal-title":"J Immunol"},{"key":"3452_CR53","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1146\/annurev-immunol-032712-095910","volume":"31","author":"JS Blum","year":"2013","unstructured":"Blum JS, Wearsch PA, Cresswell P. Pathways of antigen processing. Annu Rev Immunol. 2013;31:443\u201373.","journal-title":"Annu Rev Immunol"},{"key":"3452_CR54","doi-asserted-by":"crossref","unstructured":"Wang N, Waghray D, Caveney NA, Jude KM, Garcia KC. Structural insights into human MHC-II association with invariant chain. Proc Natl Acad Sci. 2024;121:e2403031121.","DOI":"10.1073\/pnas.2403031121"},{"key":"3452_CR55","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1038\/s41589-023-01316-3","volume":"19","author":"ET Abualrous","year":"2023","unstructured":"Abualrous ET, et al. MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange. Nat Chem Biol. 2023;19:1196\u2013204.","journal-title":"Nat Chem Biol"},{"key":"3452_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41419-023-05835-8","volume":"14","author":"R Chakraborty","year":"2023","unstructured":"Chakraborty R, Nonaka T, Hasegawa M, Zurzolo C. Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of \u03b1-synuclein and mitochondria. Cell Death Dis. 2023;14:1\u201312.","journal-title":"Cell Death Dis"},{"key":"3452_CR57","doi-asserted-by":"publisher","first-page":"103839","DOI":"10.1016\/j.mcn.2023.103839","volume":"125","author":"E Konstantinidis","year":"2023","unstructured":"Konstantinidis E, Dakhel A, Beretta C, Erlandsson A. Long-term effects of amyloid-beta deposits in human iPSC-derived astrocytes. Mol Cell Neurosci. 2023;125:103839.","journal-title":"Mol Cell Neurosci"},{"key":"3452_CR58","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12974-021-02158-3","volume":"18","author":"J Rostami","year":"2021","unstructured":"Rostami J, et al. Crosstalk between astrocytes and microglia results in increased degradation of \u03b1-synuclein and amyloid-\u03b2 aggregates. J Neuroinflamm. 2021;18:124.","journal-title":"J Neuroinflamm"},{"key":"3452_CR59","doi-asserted-by":"publisher","first-page":"108572","DOI":"10.1016\/j.celrep.2020.108572","volume":"34","author":"G Qi","year":"2021","unstructured":"Qi G, et al. ApoE4 impairs neuron-astrocyte coupling of fatty acid metabolism. Cell Rep. 2021;34:108572.","journal-title":"Cell Rep"},{"key":"3452_CR60","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s12974-022-02687-5","volume":"20","author":"E Konstantinidis","year":"2023","unstructured":"Konstantinidis E, et al. Intracellular deposits of amyloid-beta influence the ability of human iPSC-derived astrocytes to support neuronal function. J Neuroinflamm. 2023;20:3.","journal-title":"J Neuroinflamm"},{"key":"3452_CR61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41392-020-00451-w","volume":"6","author":"B Wang","year":"2021","unstructured":"Wang B, et al. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets. Sig Transduct Target Ther. 2021;6:1\u201330.","journal-title":"Sig Transduct Target Ther"},{"key":"3452_CR62","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.yexcr.2015.10.028","volume":"340","author":"RCN Melo","year":"2016","unstructured":"Melo RCN, Weller PF. Lipid droplets in leukocytes: organelles linked to inflammatory responses. Exp Cell Res. 2016;340:193\u20137.","journal-title":"Exp Cell Res"},{"key":"3452_CR63","doi-asserted-by":"publisher","first-page":"2176","DOI":"10.1016\/j.febslet.2010.03.022","volume":"584","author":"M Beller","year":"2010","unstructured":"Beller M, Thiel K, Thul PJ, J\u00e4ckle H. Lipid droplets: a dynamic organelle moves into focus. FEBS Lett. 2010;584:2176\u201382.","journal-title":"FEBS Lett"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-025-03452-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-025-03452-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-025-03452-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T12:07:14Z","timestamp":1745496434000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-025-03452-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3452"],"URL":"https:\/\/doi.org\/10.1186\/s12974-025-03452-0","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,24]]},"assertion":[{"value":"14 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Brain sections from cortex of AD patients and controls were used (kindly provided from Uppsala Biobank by Professor Irina Alafuzoff, ethical number 2012\/494).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"117"}}