Role of miR-142 in regulatory T cell development and regulating immune responses

Abstract

Abstract Regulatory T cells (Treg) are essential for maintenance of self-tolerance and prevention of autoimmune diseases. Although, Treg have been known to be regulated by the transcription factor Foxp3 but role of miRNAs that control Treg is still not yet completely understood. Here, we report that miR-142-deficient mice have reduced number of Treg, but normal development of CD4+Foxp3− T cells both in the thymus and periphery. Interestingly, reduced number of Treg was accompanied by increased frequencies and numbers of Th1 cell responses in the periphery. In addition, we found that miR-142KO T cells showed defective in-vitro Treg cell differentiation. Lastly, we compared the outcome of herpes simplex virus 1(HSV-1) induced immunopathology, Th1 cell orchestrated ocular lesions, in mice unable to express miR-142 because of gene knockout to that of wild-type mice. The miR-142KO mice developed more-severe and earlier stromal keratitis lesions than did infected wild-type animals. This increased disease severity was associated with increased Th1 cell responses in the cornea at day 7pi. Taken together our data suggests that miR-142 is required for normal Treg cell development and that proper regulation of miR-142 is crucial for immunological tolerance.