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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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.
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.
CX3CR1-deficient EAE mice were created. Disease severity, pathological damage, and the expressions of MHC-II and its mediators on myeloid cells were detected.
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).
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.
KeywordsMultiple sclerosis Experimental autoimmune encephalomyelitis CX3CR1 Major histocompatibility complex class II molecules Class II transactivator Interferon regulatory factor-1
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).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 9.Lauro C, Cipriani R, Catalano M, Trettel F, Chece G, Brusadin V, Antonilli L, van Rooijen N, Eusebi F, Fredholm BB, Limatola C (2010) Adenosine A1 receptors and microglial cells mediate CX3CL1-induced protection of hippocampal neurons against Glu-induced death. Neuropsychopharmacology 35:1550–1559CrossRefGoogle Scholar
- 12.Huang D, Shi FD, Jung S, Pien GC, Wang J, Salazar-Mather TP, He TT, Weaver JT, Ljunggren HG, Biron CA, Littman DR, Ransohoff RM (2006) The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system. FASEB J 20:896–905CrossRefGoogle Scholar
- 16.Ridderstad Wollberg A, Ericsson-Dahlstrand A, Juréus A, Ekerot P, Simon S, Nilsson M, Wiklund SJ, Berg AL, Ferm M, Sunnemark D, Johansson R (2014) Pharmacological inhibition of the chemokine receptor CX3CR1 attenuates disease in a chronic-relapsing rat model for multiple sclerosis. Proc Natl Acad Sci U S A 111:5409–5414CrossRefGoogle Scholar
- 26.Stickel N, Hanke K, Marschner D, Prinz G, Köhler M, Melchinger W, Pfeifer D, Schmitt-Graeff A, Brummer T, Heine A, Brossart P, Wolf D, von Bubnoff N, Finke J, Duyster J, Ferrara J, Salzer U, Zeiser R (2017) MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation. Leukemia 31:2732–2741CrossRefGoogle Scholar