TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions

Cell Rep. 2019 Sep 17;28(12):3077-3091.e5. doi: 10.1016/j.celrep.2019.08.050.


MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissue-repair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.

Keywords: MAIT cells; TCR signaling; cytokines; effector functions; tissue repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Caco-2 Cells
  • Cytokines / immunology
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / pathology
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / immunology*
  • THP-1 Cells


  • Cytokines
  • Receptors, Antigen, T-Cell