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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

Neurological Sciences volume 40, pages 779–791 (2019)Cite this article

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

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

Authors
  1. Weihua Mai
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  2. Xingwei Liu
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  4. Jing Zheng
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  5. Xiao Wang
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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

Keywords

  • Multiple sclerosis
  • Experimental autoimmune encephalomyelitis
  • CX3CR1
  • Major histocompatibility complex class II molecules
  • Class II transactivator
  • Interferon regulatory factor-1