Altered miR-146a expression in Sjögren's syndrome and its functional role in innate immunity

Eur J Immunol. 2011 Jul;41(7):2029-39. doi: 10.1002/eji.201040757. Epub 2011 May 27.


MicroRNAs (miRNAs), small non-coding RNA molecules that post-transcriptionally regulate gene expression, are known to play key roles in regulating immune responses and autoimmunity. We investigated miR-146a expression in Sjögren's syndrome (SjS) patients as well as in the SjS-prone C57BL/6.NOD-Aec1Aec2 mouse model, to elucidate its involvement in SjS pathogenesis. Expression of miR-146a was examined in the PBMCs of 25 SjS patients and ten healthy donors, as well as in PBMCs, salivary and lacrimal glands of SjS-prone mice and WT C57BL/6J mice. Functional assays using THP-1 human monocytes were conducted to determine the biological roles of miR-146a in innate immunity. Expression of miR-146a was significantly increased in SjS patients compared with healthy controls, and was upregulated in the salivary glands and PBMCs of the SjS-prone mouse at both 8 wk (prior to disease onset) and 20 wk (full-blown disease) of age. More importantly, functional analysis revealed roles for miR-146a in increasing phagocytic activity and suppressing inflammatory cytokine production while migration, nitric oxide production and expression of antigen-presenting/costimulatory molecules are not affected in human monocytic THP-1 cells. Taken together, our data suggest that abnormal expression/regulation of microRNAs in innate immunity may contribute to, or be indicative of, the initiation and progression of SjS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antigen Presentation
  • Chemotaxis, Leukocyte
  • Cytokines / biosynthesis
  • Female
  • Gene Expression
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Immunity, Innate*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Monocytes / immunology
  • Nitric Oxide / biosynthesis
  • Phagocytosis
  • Polymerase Chain Reaction
  • Salivary Glands / cytology
  • Salivary Glands / metabolism
  • Signal Transduction / genetics
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / metabolism
  • Young Adult


  • Cytokines
  • MIRN146 microRNA, human
  • MIRN155 microRNA, human
  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Nitric Oxide