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Article: Fatty acid binding protein 4 promotes autoimmune diabetes by recruitment and activation of pancreatic islet macrophages

TitleFatty acid binding protein 4 promotes autoimmune diabetes by recruitment and activation of pancreatic islet macrophages
Authors
KeywordsAutoimmunity
Diabetes
Endocrinology
Innate immunity
Macrophages
Issue Date2021
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at https://insight.jci.org/
Citation
JCI insight, 2021, April, v. 6 n. 7, article no. e141814 How to Cite?
AbstractBoth innate and adaptive immune cells are critical players in autoimmune destruction of insulin-producing β cells in type 1 diabetes. However, the early pathogenic events triggering the recruitment and activation of innate immune cells in islets remain obscure. Here we show that circulating fatty acid binding protein 4 (FABP4) level was significantly elevated in patients with type 1 diabetes and their first-degree relatives and positively correlated with the titers of several islet autoantibodies. In nonobese diabetic (NOD) mice, increased FABP4 expression in islet macrophages started from the neonatal period, well before the occurrence of overt diabetes. Furthermore, the spontaneous development of autoimmune diabetes in NOD mice was markedly reduced by pharmacological inhibition or genetic ablation of FABP4 or adoptive transfer of FABP4-deficient bone marrow cells. Mechanistically, FABP4 activated innate immune responses in islets by enhancing the infiltration and polarization of macrophages to proinflammatory M1 subtype, thus creating an inflammatory milieu required for activation of diabetogenic CD8+ T cells and shift of CD4+ helper T cells toward Th1 subtypes. These findings demonstrate FABP4 as a possible early mediator for β cell autoimmunity by facilitating crosstalk between innate and adaptive immune cells, suggesting that pharmacological inhibition of FABP4 may represent a promising therapeutic strategy for autoimmune diabetes.
Persistent Identifierhttp://hdl.handle.net/10722/300314
ISSN
2021 Impact Factor: 9.484
2020 SCImago Journal Rankings: 4.099
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorXiao, Y-
dc.contributor.authorShu, L-
dc.contributor.authorWu, X-
dc.contributor.authorLiu, Y-
dc.contributor.authorCheong, LY-
dc.contributor.authorLiao, B-
dc.contributor.authorXiao, Y-
dc.contributor.authorHoo, RLC-
dc.contributor.authorZhou, Z-
dc.contributor.authorXu, A-
dc.date.accessioned2021-06-04T08:41:11Z-
dc.date.available2021-06-04T08:41:11Z-
dc.date.issued2021-
dc.identifier.citationJCI insight, 2021, April, v. 6 n. 7, article no. e141814-
dc.identifier.issn2379-3708-
dc.identifier.urihttp://hdl.handle.net/10722/300314-
dc.description.abstractBoth innate and adaptive immune cells are critical players in autoimmune destruction of insulin-producing β cells in type 1 diabetes. However, the early pathogenic events triggering the recruitment and activation of innate immune cells in islets remain obscure. Here we show that circulating fatty acid binding protein 4 (FABP4) level was significantly elevated in patients with type 1 diabetes and their first-degree relatives and positively correlated with the titers of several islet autoantibodies. In nonobese diabetic (NOD) mice, increased FABP4 expression in islet macrophages started from the neonatal period, well before the occurrence of overt diabetes. Furthermore, the spontaneous development of autoimmune diabetes in NOD mice was markedly reduced by pharmacological inhibition or genetic ablation of FABP4 or adoptive transfer of FABP4-deficient bone marrow cells. Mechanistically, FABP4 activated innate immune responses in islets by enhancing the infiltration and polarization of macrophages to proinflammatory M1 subtype, thus creating an inflammatory milieu required for activation of diabetogenic CD8+ T cells and shift of CD4+ helper T cells toward Th1 subtypes. These findings demonstrate FABP4 as a possible early mediator for β cell autoimmunity by facilitating crosstalk between innate and adaptive immune cells, suggesting that pharmacological inhibition of FABP4 may represent a promising therapeutic strategy for autoimmune diabetes.-
dc.languageeng-
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at https://insight.jci.org/-
dc.relation.ispartofJCI insight-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAutoimmunity-
dc.subjectDiabetes-
dc.subjectEndocrinology-
dc.subjectInnate immunity-
dc.subjectMacrophages-
dc.titleFatty acid binding protein 4 promotes autoimmune diabetes by recruitment and activation of pancreatic islet macrophages-
dc.typeArticle-
dc.identifier.emailWu, X: raxpwu@hku.hk-
dc.identifier.emailCheong, LY: u3003285@connect.hku.hk-
dc.identifier.emailLiao, B: babylia@hku.hk-
dc.identifier.emailHoo, RLC: rubyhoo@hkucc.hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityHoo, RLC=rp01334-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1172/jci.insight.141814-
dc.identifier.pmid33690220-
dc.identifier.pmcidPMC8119222-
dc.identifier.scopuseid_2-s2.0-85104160308-
dc.identifier.hkuros322717-
dc.identifier.issue7-
dc.identifier.spagearticle no. e141814-
dc.identifier.epagearticle no. e141814-
dc.identifier.isiWOS:000638250400007-
dc.publisher.placeUnited States-

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