MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients

Takuya Niimoto1, Tomoyuki Nakasa, Masakazu Ishikawa

  • 1Department of Orthopaedic Surgery, Programs for Applied Biomedicine, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551 Japan. tnakasa@smn.enjoy.ne.jp

Abstract

Insights

MicroRNA-146a is linked to Interleukin-17 in rheumatoid arthritis (RA) patients. This microRNA may play a role in regulating IL-17 expression within immune cells and joint tissues.

Area of Science:

  • Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • Interleukin-17 (IL-17) is a key factor in rheumatoid arthritis (RA) pathogenesis.
  • MicroRNAs (miRNAs) are implicated in various human diseases, including RA.

Purpose of the Study:

  • Identify miRNAs involved in IL-17-producing cell differentiation.
  • Analyze miRNA expression patterns in peripheral blood mononuclear cells (PBMCs) and synovium from RA patients.

Main Methods:

  • Expansion of IL-17-producing CD4+ T cells.
  • miRNA microarray analysis to identify key miRNAs.
  • Quantitative PCR and double staining (in situ hybridization/immunohistochemistry) to assess miRNA and IL-17 expression in patient samples.

Main Results:

  • Six miRNAs (let-7a, miR-26, miR-146a/b, miR-150, miR-155) were upregulated in IL-17-producing T cells.
  • miR-146a and IL-17 expression was higher in PBMCs of RA patients with lower disease severity.
  • miR-146a showed intense expression in RA synovium compared to osteoarthritis (OA), particularly in inflamed tissues with high IL-17 levels.

Conclusions:

  • miR-146a is associated with IL-17 expression in both PBMCs and synovium of RA patients.
  • miR-146a may participate in the regulation of IL-17 expression in RA.

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...