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Interferon‐ β regulates dendritic cell activation and migration in experimental autoimmune encephalomyelitis
Author(s) -
Pennell Leesa M.,
Fish Eleanor N.
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12781
Subject(s) - myelin oligodendrocyte glycoprotein , experimental autoimmune encephalomyelitis , immunology , biology , stat protein , t cell , cd11c , adoptive cell transfer , multiple sclerosis , encephalomyelitis , dendritic cell , rar related orphan receptor gamma , interferon , antigen , immune system , microbiology and biotechnology , signal transduction , stat3 , foxp3 , biochemistry , gene , phenotype
Summary CD11c + dendritic cells ( DC s) exert a critical role as antigen‐presenting cells in regulating pathogenic T cells in multiple sclerosis ( MS ). To determine whether the therapeutic benefit of interferon‐ β ( IFN ‐ β ) treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DC s derived from IFN ‐ β +/+ and IFN ‐ β −/− mice using a myelin oligodendrocyte glycoprotein ( MOG ) peptide‐induced mouse model of MS , experimental autoimmune encephalomyelitis ( EAE ). Our earlier work identified that IFN ‐ β −/− mice exhibit earlier onset and more rapid progression of neurological impairment compared with IFN ‐ β +/+ mice. In this study we show that lipopolysaccharide‐/ MOG peptide‐stimulated IFN ‐ β −/− DC s secrete cytokines associated with pathological T helper type 17 rather than regulatory T‐cell polarization and exhibit increased CD 80 and MHCII expression when compared with stimulated IFN ‐ β +/+ DC s. IFN ‐ β −/− DC s from mice immunized to develop EAE induce greater proliferation of MOG ‐transgenic CD 4 + T cells and promote interleukin‐17 production by these T cells. Adoptive transfer of MOG peptide‐primed IFN ‐ β −/− DC s into IFN ‐ β +/+ and IFN ‐ β −/− mice immunized to develop EAE resulted in their rapid migration into the central nervous system of recipient mice, before onset of disease, which we attribute to failed signal transducer and activator of transcription 1‐mediated inhibition of CCR 7. Taken together, our data support immunoregulatory roles for IFN ‐ β in the activation and migration of DC s during EAE .