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Inverse correlation of expression of microRNA‐140‐5p with progression of multiple sclerosis and differentiation of encephalitogenic T helper type 1 cells
Author(s) -
Guan Hongbing,
Singh Udai P.,
Rao Roshni,
Mrelashvili Davit,
Sen Souvik,
Hao Haiping,
Zumbrun Elizabeth E.,
Singh Narendra P.,
Nagarkatti Prakash S.,
Nagarkatti Mitzi
Publication year - 2016
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.12583
Subject(s) - microrna , pathogenesis , peripheral blood mononuclear cell , transfection , multiple sclerosis , biology , stat1 , stat protein , cellular differentiation , immunology , gene expression , t cell , microbiology and biotechnology , gene , signal transduction , immune system , stat3 , genetics , in vitro
Summary The role of micro RNA in the regulation of encephalitogenic T‐cell development is of interest in understanding the pathogenesis of multiple sclerosis ( MS ). Direct binding of microRNAs to their target mRNA s usually suppresses gene expression and facilitates mRNA degradation. In this study, we observed that the expression of several microRNAs was significantly altered in patients with MS . Interestingly, the expression of miR‐140‐5p, among other microRNAs, was significantly decreased in the peripheral blood mononuclear cells of patients with MS , and this microRNA may regulate encephalitogenic T helper type 1 (Th1) cell differentiation. The expression level of miR‐140‐5p was inversely correlated with disease severity with greater reduction in relapsing disease compared with remitting disease. Transfection of synthetic miR‐140‐5p in peripheral blood mononuclear cells suppressed encephalitogenic Th1 differentiation. Signal transducer and activator of transcription 1 (STAT1) was the functional target of miR‐140‐5p – transfection of the synthetic miR‐140‐5p suppressed activation of STAT1 and the expression of its downstream target, T‐bet. Our results suggested that miR‐140‐5p is probably involved in the regulation of encephalitogenic T cells in the pathogenesis of MS.