Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T H17 cells in the intestine

Michael H. Shaw, Nobuhiko Kamada, Yungi Kim, Gabriel Núñez

Research output: Contribution to journalArticle

191 Citations (Scopus)

Abstract

T H17 cells are a lineage of CD4+ T cells that are critical for host defense and autoimmunity by expressing the cytokines IL-17A, IL-17F, and IL-22. A feature of T H17 cells at steady state is their ubiquitous presence in the lamina propria of the small intestine. The induction of these steady-state intestinal T H17 (sT H17) cells is dependent on the presence of the microbiota. However, the signaling pathway linking the microbiota to the development of intestinal sT H17 cells remains unclear. In this study, we show that IL-1β, but not IL-6, is induced by the presence of the microbiota in intestinal macrophages and is required for the induction of sT H17 cells. In the absence of IL-1β-IL-1R or MyD88 signaling, there is a selective reduction in the frequency of intestinal sT H17 cells and impaired production of IL-17 and IL-22. Myeloid differentiation factor 88-deficient (MyD88 -/-) and germ-free (GF) mice, but not IL-1R -/- mice, exhibit impairment in IL-1β induction. Microbiota-induced IL-1β acts directly on IL-1R-expressing T cells to drive the generation of sT H17 cells. Furthermore, administration of IL-1β into GF mice induces the development of retinoic acid receptor-related orphan receptor γt-expressing sT H17 cells in the small intestine, but not in the spleen. Thus, commensal-induced IL-1β production is a critical step for sT H17 differentiation in the intestine, which may have therapeutic implications for T H17-mediated pathologies.

Original languageEnglish
Pages (from-to)251-258
Number of pages8
JournalJournal of Experimental Medicine
Volume209
Issue number2
DOIs
Publication statusPublished - 2012 Feb
Externally publishedYes

Fingerprint

Microbiota
Interleukin-1
Intestines
Interleukin-6
Interleukin-17
Small Intestine
Myeloid Differentiation Factor 88
T-Lymphocytes
Retinoic Acid Receptors
Cell Lineage
Autoimmunity
Mucous Membrane
Spleen
Macrophages
Pathology
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T H17 cells in the intestine. / Shaw, Michael H.; Kamada, Nobuhiko; Kim, Yungi; Núñez, Gabriel.

In: Journal of Experimental Medicine, Vol. 209, No. 2, 02.2012, p. 251-258.

Research output: Contribution to journalArticle

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