Production of IL-17 by MAIT Cells Is Increased in Multiple Sclerosis and Is Associated with IL-7 Receptor Expression

J Immunol. 2018 Feb 1;200(3):974-982. doi: 10.4049/jimmunol.1701213. Epub 2018 Jan 3.


Multiple sclerosis (MS) is a T cell-driven inflammatory disease of the CNS. Research on T cell subsets involved in MS pathogenesis has mainly focused on classical CD4+ T cells, especially Th17 cells, as they produce the proinflammatory, MS-associated cytokine IL-17. However, the abundant unconventional mucosal-associated invariant T (MAIT) cells are also able to produce IL-17. MAIT cells are characterized by high CD161 expression and a semi-invariant Vα7.2 TCR, with which they recognize bacterial and yeast Ags derived from the riboflavin (vitamin B2) metabolism. In this study, we characterized MAIT cells from the peripheral blood of MS patients in comparison with healthy individuals with respect to their type-17 differentiation. We found a specific increase of IL-17+ MAIT cells as well as an increased expression of retinoic acid-related orphan receptor (ROR)γt and CCR6 in MAIT cells from MS patients, whereas the expression of T cell activation markers HLA-DR and CD38 was not different. IL-17 production by MAIT cells furthermore correlated with the surface expression level of the IL-7 receptor α-chain (CD127), which was significantly increased on MAIT cells from MS patients in comparison with healthy individuals. In summary, our findings indicate an augmented type-17 differentiation of MAIT cells in MS patients associated with their IL-7 receptor surface expression, implicating a proinflammatory role of these unconventional T cells in MS immunopathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Central Nervous System / immunology
  • Central Nervous System / pathology*
  • HLA-DR Antigens / metabolism
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-17 / biosynthesis*
  • Interleukin-7 Receptor alpha Subunit / biosynthesis*
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / metabolism
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / metabolism
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*
  • NK Cell Lectin-Like Receptor Subfamily B / biosynthesis
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / biosynthesis
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, CCR6 / biosynthesis
  • STAT3 Transcription Factor / metabolism
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction / immunology
  • Tumor Suppressor Proteins / metabolism


  • CCR6 protein, human
  • HLA-DR Antigens
  • IL17A protein, human
  • IL7R protein, human
  • Interleukin-17
  • Interleukin-7 Receptor alpha Subunit
  • KLRB1 protein, human
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily B
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Antigen, T-Cell
  • Receptors, CCR6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Tumor Suppressor Proteins
  • Interferon-gamma
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1