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. 2019 Apr;40(4):779-791. doi: 10.1007/s10072-019-3721-2. Epub 2019 Jan 23.

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.

Keywords: CX3CR1; Class II transactivator; Experimental autoimmune encephalomyelitis; Interferon regulatory factor-1; Major histocompatibility complex class II molecules; Multiple sclerosis.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / metabolism*
  • CX3C Chemokine Receptor 1 / deficiency
  • CX3C Chemokine Receptor 1 / metabolism*
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Encephalomyelitis, Autoimmune, Experimental* / pathology
  • Encephalomyelitis, Autoimmune, Experimental* / physiopathology
  • Female
  • Histocompatibility Antigens Class II / metabolism*
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Inflammation* / physiopathology
  • Interferon Regulatory Factor-1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis* / metabolism
  • Multiple Sclerosis* / pathology
  • Multiple Sclerosis* / physiopathology
  • Myeloid Cells / metabolism
  • Nuclear Proteins / metabolism*
  • Trans-Activators / metabolism*

Substances

  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Histocompatibility Antigens Class II
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Trans-Activators