Thymic self-reactivity selects natural interleukin 17-producing T cells that can regulate peripheral inflammation

Nat Immunol. 2009 Oct;10(10):1125-32. doi: 10.1038/ni.1783. Epub 2009 Sep 6.

Abstract

Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T(H)-17 cells) share a developmental relationship with Foxp3(+) regulatory T cells (T(reg) cells). Here we show that a T(H)-17 population differentiates in the thymus in a manner influenced by recognition of self antigen and by the cytokines IL-6 and transforming growth factor-beta (TGF-beta). Like previously described T(H)-17 cells, the T(H)-17 cells that developed in the thymus expressed the transcription factor RORgamma t and the IL-23 receptor. These cells also expressed alpha(4)beta(1) integrins and the chemokine receptor CCR6 and were recruited to the lung, gut and liver. In the liver, these cells secreted IL-22 in response to self antigen and mediated host protection during inflammation. Thus, T(H)-17 cells, like T(reg) cells, can be selected by self antigens in the thymus.

Publication types

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

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Inflammation / immunology
  • Integrin alpha4beta1 / biosynthesis
  • Interleukin-17 / metabolism*
  • Interleukin-23 / biosynthesis
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Interleukins / metabolism
  • Mice
  • Mice, Transgenic
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Polymerase Chain Reaction
  • Receptors, CCR6 / biosynthesis
  • Receptors, Retinoic Acid / biosynthesis
  • Receptors, Thyroid Hormone / biosynthesis
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • Thymus Gland / cytology*
  • Thymus Gland / immunology
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism

Substances

  • Autoantigens
  • CCR6 protein, mouse
  • Integrin alpha4beta1
  • Interleukin-17
  • Interleukin-23
  • Interleukin-6
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, CCR6
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • Transforming Growth Factor beta
  • interleukin-22