IFNA-AS1 regulates CD4+ T cell activation in myasthenia gravis though HLA-DRB1

Clin Immunol. 2017 Oct:183:121-131. doi: 10.1016/j.clim.2017.08.008. Epub 2017 Aug 16.

Abstract

Abnormal CD4+T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4+ T cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. IFNG-AS1 influenced Th1/Treg cell proliferation and regulated the expression levels of their transcription factors in an experimental autoimmune myasthenia gravis (EAMG)model. IFNG-AS1 could reduce the expression of HLA-DRB and HLA-DOB and they had a negative correlation in MG. Furthermore IFNG-AS1 influenced the expression levels of CD40L and CD4+ T cells activation in MG patient partly depend on effecting the HLA-DRB1 expression. It suggests that IFNG-AS1 may be involved in CD4+T cell-mediated immune responses in MG.

Keywords: CD4(+); HLA-DOB; HLA-DRB1; IFNG-AS1; Long non-coding RNAs (lncRNAs); Myasthenia gravis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Ligand / immunology
  • Case-Control Studies
  • Cell Proliferation*
  • Female
  • HLA-D Antigens / immunology
  • HLA-DRB1 Chains / immunology
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Myasthenia Gravis / immunology*
  • Myasthenia Gravis, Autoimmune, Experimental / immunology*
  • RNA, Long Noncoding / immunology*
  • RNA, Long Noncoding / pharmacology
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / immunology*
  • Young Adult

Substances

  • HLA-D Antigens
  • HLA-DO antigens
  • HLA-DRB1 Chains
  • RNA, Long Noncoding
  • long non-coding RNA IFNA-AS1, human
  • CD40 Ligand