Unlike αβ T cells, γδ T cells, LTi cells and NKT cells do not require IRF4 for the production of IL-17A and IL-22

Eur J Immunol. 2012 Dec;42(12):3189-201. doi: 10.1002/eji.201142155. Epub 2012 Oct 17.

Abstract

Apart from conventional CD4(+) Th17 cells, the cytokines IL-17A and IL-22 can also be produced by γδ T cells, NK cells and lymphoid tissue inducer (LTi) cells. Th17 cells develop from precursor cells after T-cell receptor stimulation in the presence of TGF-β, IL-6 and IL-23. In contrast, a subset of γδ T cells ("γδT17") is committed for fast IL-17 production already in the thymus; however, γδ T cells can also produce IL-17 after prolonged in vitro stimulation via their γδ T-cell receptor plus IL-23. Here, we show that γδ T-, LTi- and NKT cells differ extensively from Th17 cells in their signalling requirements for the generation of IL-17A and IL-22. While production of these cytokines by Th17 cells totally depends on the transcription factor interferon regulatory factor 4 (IRF4), IRF4 is irrelevant in the other cell types. As for γδ T cells, this finding pertains to both thymic commitment and prolonged in vitro culture. Furthermore, IL-17A-producing γδ T cells accumulate in the central nervous system of IRF4 deficient (Irf4(-/-)) mice during experimental autoimmune encephalomyelitis. IL-17A-producing WT and Irf4(-/-) γδ T cells equally express CCR6 and lack CD27. The underlying IRF4-independent pathway partially involves STAT3 during in vitro stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / immunology
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Encephalomyelitis, Autoimmune, Experimental
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology*
  • Interferon Regulatory Factors / metabolism
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-22
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Interleukins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Natural Killer T-Cells / pathology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Receptors, CCR6 / biosynthesis
  • Receptors, CCR6 / genetics
  • Receptors, CCR6 / immunology
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology
  • STAT3 Transcription Factor / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Th17 Cells / pathology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / biosynthesis
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology

Substances

  • CCR6 protein, mouse
  • Il17a protein, mouse
  • Interferon Regulatory Factors
  • Interleukin-17
  • Interleukins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, CCR6
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • interferon regulatory factor-4