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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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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