Inverse correlation of expression of microRNA-140-5p with progression of multiple sclerosis and differentiation of encephalitogenic T helper type 1 cells

Hongbing Guan, Udai P. Singh, Roshni Rao, Davit Mrelashvili, Souvik Sen, Haiping Hao, Elizabeth E. Zumbrun, Narendra P. Singh, Prakash S. Nagarkatti, Mitzi Nagarkatti

Research output: Contribution to journalArticlepeer-review

Abstract

The role of microRNA 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 mRNAs 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.

Original languageEnglish (US)
Pages (from-to)488-498
Number of pages11
JournalImmunology
Volume147
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • Cell differentiation
  • MiR-140-5p
  • MicroRNA
  • Multiple sclerosis
  • Th1/Th2 cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Inverse correlation of expression of microRNA-140-5p with progression of multiple sclerosis and differentiation of encephalitogenic T helper type 1 cells'. Together they form a unique fingerprint.

Cite this