Restricted microbiota and absence of cognate TCR antigen leads to an unbalanced generation of Th17 cells

J Immunol. 2011 Feb 1;186(3):1531-7. doi: 10.4049/jimmunol.1001723. Epub 2010 Dec 22.

Abstract

Retinoic acid-related orphan receptor (ROR)γt(+) TCRαβ(+) cells expressing IL-17, termed Th17 cells, are most abundant in the intestinal lamina propria. Symbiotic microbiota are required for the generation of Th17 cells, but the requirement for microbiota-derived Ag is not documented. In this study, we show that normal numbers of Th17 cells develop in the intestine of mice that express a single TCR in the absence of cognate Ag, whereas the microbiota remains essential for their development. However, such mice, or mice monocolonized with the Th17-inducing segmented filamentous bacteria, fail to induce normal numbers of Foxp3(+) RORγt(+) T cells, the regulatory counterpart of IL-17(+)RORγt(+) T cells. These results demonstrate that a complex microbiota and cognate Ag are required to generate a properly regulated set of RORγt(+) T cells and Th17 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4 Lymphocyte Count
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Proliferation*
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / deficiency
  • Forkhead Transcription Factors / genetics
  • Germ-Free Life / genetics
  • Germ-Free Life / immunology
  • Gram-Positive Bacterial Infections / immunology
  • Gram-Positive Bacterial Infections / pathology
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / biosynthesis
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / deficiency*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Receptors, Antigen, T-Cell / deficiency*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / physiology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / microbiology*
  • T-Lymphocytes, Helper-Inducer / pathology

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, Antigen, T-Cell
  • Rorc protein, mouse
  • Green Fluorescent Proteins