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Protective effects of CX3CR1 on autoimmune inflammation in a chronic EAE model for MS through modulation of antigen-presenting cell-related molecular MHC-II and its regulators

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Abstract

Background

Recent evidences have implicated neuroprotective effects of CX3CR1 in multiple sclerosis (MS). But whether CX3CR1 is involved in modulation of antigen-presenting cell (APC)–related molecular MHC-II and what the possible mechanism is remain unidentified.

Objective

In this study, we intended to investigate the effects of CX3CR1 on MHC-II expressions on brain myeloid cells in experimental autoimmune encephalomyelitis (EAE) mice and explore the possible regulators for it.

Methods

CX3CR1-deficient EAE mice were created. Disease severity, pathological damage, and the expressions of MHC-II and its mediators on myeloid cells were detected.

Results

We found that compare with wile-typed EAE mice, CX3CR1-deficient EAE mice exhibited more severe disease severity. An accumulation of CD45+CD115+Ly6C−CD11c+ cells was reserved in the affected EAE brain of CX3CR1-deficient mice, consistent with disease severity and pathological damage in the brain. The expressions of MHC-II on the brain CD45+CD115+Ly6C−CD11c+ cells of CX3CR1-deficient EAE mice were elevated, in accord with the increased protein and mRNA expressions of class II transactivator (CIITA) and interferon regulatory factor-1 (IRF-1).

Conclusions

The findings indicated that CX3CR1 might be an important regulator for MHC-II expressions on APCs, playing a beneficial role in EAE. The mechanism was probably through regulation on the MHC-II regulators CIITA and IRF-1.

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Funding

This work was supported by the Natural Science Foundation of Guangdong Province, China (Grant No: 2014A030313028), and Science and Technology Planning Project of Zhuhai city, China (Grant No: 2015A1011).

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Author notes

  1. Weihua Mai and Xingwei Liu contributed equally to this work and should be considered co-first author

Authors and Affiliations

  1. Department of Neurology, The Fifth Affiliated Hospital of Sun Yat-sen University, NO. 52 East Meihua Road, Zhuhai, 519000, Guangdong Province, China

    Weihua Mai & Junfeng Wang

  2. Department of General Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China

    Xingwei Liu & Xiao Wang

  3. Department of Nephrology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China

    Jing Zheng

  4. Department of Laboratory Science, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China

    Wenying Zhou

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  1. Weihua Mai
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  4. Jing Zheng
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Correspondence to Weihua Mai.

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Mai, W., Liu, X., Wang, J. et al. Protective effects of CX3CR1 on autoimmune inflammation in a chronic EAE model for MS through modulation of antigen-presenting cell-related molecular MHC-II and its regulators. Neurol Sci 40, 779–791 (2019). https://doi.org/10.1007/s10072-019-3721-2

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  • DOI: https://doi.org/10.1007/s10072-019-3721-2

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