Frontiers in Immunology (Dec 2018)

MicroRNA-31 Reduces the Motility of Proinflammatory T Helper 1 Lymphocytes

  • Markus Bardua,
  • Claudia Haftmann,
  • Pawel Durek,
  • Kerstin Westendorf,
  • Antje Buttgereit,
  • Cam Loan Tran,
  • Mairi McGrath,
  • Melanie Weber,
  • Katrin Lehmann,
  • Richard Kwasi Addo,
  • Gitta Anne Heinz,
  • Anna-Barbara Stittrich,
  • Patrick Maschmeyer,
  • Helena Radbruch,
  • Michael Lohoff,
  • Hyun-Dong Chang,
  • Andreas Radbruch,
  • Mir-Farzin Mashreghi

DOI
https://doi.org/10.3389/fimmu.2018.02813
Journal volume & issue
Vol. 9

Abstract

Read online

Proinflammatory type 1 T helper (Th1) cells are enriched in inflamed tissues and contribute to the maintenance of chronic inflammation in rheumatic diseases. Here we show that the microRNA- (miR-) 31 is upregulated in murine Th1 cells with a history of repeated reactivation and in memory Th cells isolated from the synovial fluid of patients with rheumatic joint disease. Knock-down of miR-31 resulted in the upregulation of genes associated with cytoskeletal rearrangement and motility and induced the expression of target genes involved in T cell activation, chemokine receptor– and integrin-signaling. Accordingly, inhibition of miR-31 resulted in increased migratory activity of repeatedly activated Th1 cells. The transcription factors T-bet and FOXO1 act as positive and negative regulators of T cell receptor (TCR)–mediated miR-31 expression, respectively. Taken together, our data show that a gene regulatory network involving miR-31, T-bet, and FOXO1 controls the migratory behavior of proinflammatory Th1 cells.

Keywords