Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells Infiltration

Growing evidence suggests that obesity is associated with the susceptibility and disease severity of multiple sclerosis. The chronic inflammation induced by obesity is believed to contribute to this process. However, the immune mechanisms connecting obesity to the prevalence and pathogenesis of MS a...

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Main Authors: Zhe Ji, Shuai Wu, Yaru Xu, Jingjing Qi, Xiaohui Su, Lei Shen
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-08-01
Series:Frontiers in Immunology
Subjects:
EAE
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.01881/full
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spelling doaj-553a4c55a2d04380ada6e0ef33437e7b2020-11-25T01:55:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-08-011010.3389/fimmu.2019.01881468686Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells InfiltrationZhe Ji0Zhe Ji1Shuai Wu2Yaru Xu3Jingjing Qi4Xiaohui Su5Lei Shen6Translational Medicine Research Center, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaGrowing evidence suggests that obesity is associated with the susceptibility and disease severity of multiple sclerosis. The chronic inflammation induced by obesity is believed to contribute to this process. However, the immune mechanisms connecting obesity to the prevalence and pathogenesis of MS are poorly defined. In this study, we show that high fat diet (HFD)-induced obese mice developed an exacerbated EAE as indicated by higher clinical scores and more severe pathological changes in spinal cord than the control mice fed with normal diet (ND), following immunization with myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide. The exacerbation of EAE in HFD mice was associated with enhanced microglial activation and increased expansion of Th1 and Th17 cells. The HFD mice also showed aggravated disease in an adoptive T cell transfer EAE model. Mechanistically, HFD augmented the expression level of IL-6 and CCL-2 both in serum and brain, and blockade of IL-6 and CCL-2 signal ameliorated EAE with reduced T cells infiltration in CNS. Taken together, our results suggest that obesity promotes CNS inflammation in EAE through IL-6 and CCL-2 mediated the inflammatory cells infiltration.https://www.frontiersin.org/article/10.3389/fimmu.2019.01881/fullobesityEAEinfiltration of T lymphocyteCCL-2IL-6
collection DOAJ
language English
format Article
sources DOAJ
author Zhe Ji
Zhe Ji
Shuai Wu
Yaru Xu
Jingjing Qi
Xiaohui Su
Lei Shen
spellingShingle Zhe Ji
Zhe Ji
Shuai Wu
Yaru Xu
Jingjing Qi
Xiaohui Su
Lei Shen
Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells Infiltration
Frontiers in Immunology
obesity
EAE
infiltration of T lymphocyte
CCL-2
IL-6
author_facet Zhe Ji
Zhe Ji
Shuai Wu
Yaru Xu
Jingjing Qi
Xiaohui Su
Lei Shen
author_sort Zhe Ji
title Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells Infiltration
title_short Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells Infiltration
title_full Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells Infiltration
title_fullStr Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells Infiltration
title_full_unstemmed Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells Infiltration
title_sort obesity promotes eae through il-6 and ccl-2-mediated t cells infiltration
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2019-08-01
description Growing evidence suggests that obesity is associated with the susceptibility and disease severity of multiple sclerosis. The chronic inflammation induced by obesity is believed to contribute to this process. However, the immune mechanisms connecting obesity to the prevalence and pathogenesis of MS are poorly defined. In this study, we show that high fat diet (HFD)-induced obese mice developed an exacerbated EAE as indicated by higher clinical scores and more severe pathological changes in spinal cord than the control mice fed with normal diet (ND), following immunization with myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide. The exacerbation of EAE in HFD mice was associated with enhanced microglial activation and increased expansion of Th1 and Th17 cells. The HFD mice also showed aggravated disease in an adoptive T cell transfer EAE model. Mechanistically, HFD augmented the expression level of IL-6 and CCL-2 both in serum and brain, and blockade of IL-6 and CCL-2 signal ameliorated EAE with reduced T cells infiltration in CNS. Taken together, our results suggest that obesity promotes CNS inflammation in EAE through IL-6 and CCL-2 mediated the inflammatory cells infiltration.
topic obesity
EAE
infiltration of T lymphocyte
CCL-2
IL-6
url https://www.frontiersin.org/article/10.3389/fimmu.2019.01881/full
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