Brendan Cordeiro, Jeeyoon Jennifer Ahn, Saurabh Gawde, Carmen Ucciferri, Nuria Alvarez-Sanchez, Xavier S Revelo, Natalie Stickle, Kaylea Massey, David G Brooks, Joel M Guthridge, Gabriel Pardo, Daniel A Winer, Robert C Axtell, Shannon E Dunn
{"title":"肥胖会强化性别特异性干扰素信号,从而选择性地恶化女性中枢神经系统自身免疫。","authors":"Brendan Cordeiro, Jeeyoon Jennifer Ahn, Saurabh Gawde, Carmen Ucciferri, Nuria Alvarez-Sanchez, Xavier S Revelo, Natalie Stickle, Kaylea Massey, David G Brooks, Joel M Guthridge, Gabriel Pardo, Daniel A Winer, Robert C Axtell, Shannon E Dunn","doi":"10.1016/j.cmet.2024.07.017","DOIUrl":null,"url":null,"abstract":"<p><p>Obesity has been implicated in the rise of autoimmunity in women. We report that obesity induces a serum protein signature that is associated with T helper 1 (Th1), interleukin (IL)-17, and multiple sclerosis (MS) signaling pathways selectively in human females. Females, but not male mice, subjected to diet-induced overweightness/obesity (DIO) exhibited upregulated Th1/IL-17 inflammation in the central nervous system during experimental autoimmune encephalomyelitis, a model of MS. This was associated with worsened disability and a heightened expansion of myelin-specific Th1 cells in the peripheral lymphoid organs. Moreover, at steady state, DIO increased serum levels of interferon (IFN)-α and potentiated STAT1 expression and IFN-γ production by naive CD4<sup>+</sup> T cells uniquely in female mice. This T cell phenotype was driven by increased adiposity and was prevented by the removal of ovaries or knockdown of the type I IFN receptor in T cells. Our findings offer a mechanistic explanation of how obesity enhances autoimmunity.</p>","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":" ","pages":"2298-2314.e11"},"PeriodicalIF":0.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463735/pdf/","citationCount":"0","resultStr":"{\"title\":\"Obesity intensifies sex-specific interferon signaling to selectively worsen central nervous system autoimmunity in females.\",\"authors\":\"Brendan Cordeiro, Jeeyoon Jennifer Ahn, Saurabh Gawde, Carmen Ucciferri, Nuria Alvarez-Sanchez, Xavier S Revelo, Natalie Stickle, Kaylea Massey, David G Brooks, Joel M Guthridge, Gabriel Pardo, Daniel A Winer, Robert C Axtell, Shannon E Dunn\",\"doi\":\"10.1016/j.cmet.2024.07.017\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Obesity has been implicated in the rise of autoimmunity in women. We report that obesity induces a serum protein signature that is associated with T helper 1 (Th1), interleukin (IL)-17, and multiple sclerosis (MS) signaling pathways selectively in human females. Females, but not male mice, subjected to diet-induced overweightness/obesity (DIO) exhibited upregulated Th1/IL-17 inflammation in the central nervous system during experimental autoimmune encephalomyelitis, a model of MS. This was associated with worsened disability and a heightened expansion of myelin-specific Th1 cells in the peripheral lymphoid organs. Moreover, at steady state, DIO increased serum levels of interferon (IFN)-α and potentiated STAT1 expression and IFN-γ production by naive CD4<sup>+</sup> T cells uniquely in female mice. This T cell phenotype was driven by increased adiposity and was prevented by the removal of ovaries or knockdown of the type I IFN receptor in T cells. Our findings offer a mechanistic explanation of how obesity enhances autoimmunity.</p>\",\"PeriodicalId\":93927,\"journal\":{\"name\":\"Cell metabolism\",\"volume\":\" \",\"pages\":\"2298-2314.e11\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463735/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell metabolism\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cmet.2024.07.017\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.cmet.2024.07.017","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/20 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Obesity intensifies sex-specific interferon signaling to selectively worsen central nervous system autoimmunity in females.
Obesity has been implicated in the rise of autoimmunity in women. We report that obesity induces a serum protein signature that is associated with T helper 1 (Th1), interleukin (IL)-17, and multiple sclerosis (MS) signaling pathways selectively in human females. Females, but not male mice, subjected to diet-induced overweightness/obesity (DIO) exhibited upregulated Th1/IL-17 inflammation in the central nervous system during experimental autoimmune encephalomyelitis, a model of MS. This was associated with worsened disability and a heightened expansion of myelin-specific Th1 cells in the peripheral lymphoid organs. Moreover, at steady state, DIO increased serum levels of interferon (IFN)-α and potentiated STAT1 expression and IFN-γ production by naive CD4+ T cells uniquely in female mice. This T cell phenotype was driven by increased adiposity and was prevented by the removal of ovaries or knockdown of the type I IFN receptor in T cells. Our findings offer a mechanistic explanation of how obesity enhances autoimmunity.