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Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine

T(H)17 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(H)17 cells at steady state is their ubiquitous presence in the lamina propria of the small intestine. The induction of these steady-s...

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Autores principales: Shaw, Michael H., Kamada, Nobuhiko, Kim, Yun-Gi, Núñez, Gabriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280878/
https://www.ncbi.nlm.nih.gov/pubmed/22291094
http://dx.doi.org/10.1084/jem.20111703
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author Shaw, Michael H.
Kamada, Nobuhiko
Kim, Yun-Gi
Núñez, Gabriel
author_facet Shaw, Michael H.
Kamada, Nobuhiko
Kim, Yun-Gi
Núñez, Gabriel
author_sort Shaw, Michael H.
collection PubMed
description T(H)17 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(H)17 cells at steady state is their ubiquitous presence in the lamina propria of the small intestine. The induction of these steady-state intestinal T(H)17 (sT(H)17) cells is dependent on the presence of the microbiota. However, the signaling pathway linking the microbiota to the development of intestinal sT(H)17 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(H)17 cells. In the absence of IL-1β–IL-1R or MyD88 signaling, there is a selective reduction in the frequency of intestinal sT(H)17 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(H)17 cells. Furthermore, administration of IL-1β into GF mice induces the development of retinoic acid receptor–related orphan receptor γt–expressing sT(H)17 cells in the small intestine, but not in the spleen. Thus, commensal-induced IL-1β production is a critical step for sT(H)17 differentiation in the intestine, which may have therapeutic implications for T(H)17-mediated pathologies.
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spelling pubmed-32808782012-08-13 Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine Shaw, Michael H. Kamada, Nobuhiko Kim, Yun-Gi Núñez, Gabriel J Exp Med Brief Definitive Report T(H)17 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(H)17 cells at steady state is their ubiquitous presence in the lamina propria of the small intestine. The induction of these steady-state intestinal T(H)17 (sT(H)17) cells is dependent on the presence of the microbiota. However, the signaling pathway linking the microbiota to the development of intestinal sT(H)17 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(H)17 cells. In the absence of IL-1β–IL-1R or MyD88 signaling, there is a selective reduction in the frequency of intestinal sT(H)17 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(H)17 cells. Furthermore, administration of IL-1β into GF mice induces the development of retinoic acid receptor–related orphan receptor γt–expressing sT(H)17 cells in the small intestine, but not in the spleen. Thus, commensal-induced IL-1β production is a critical step for sT(H)17 differentiation in the intestine, which may have therapeutic implications for T(H)17-mediated pathologies. The Rockefeller University Press 2012-02-13 /pmc/articles/PMC3280878/ /pubmed/22291094 http://dx.doi.org/10.1084/jem.20111703 Text en © 2012 Shaw et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Shaw, Michael H.
Kamada, Nobuhiko
Kim, Yun-Gi
Núñez, Gabriel
Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine
title Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine
title_full Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine
title_fullStr Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine
title_full_unstemmed Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine
title_short Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state T(H)17 cells in the intestine
title_sort microbiota-induced il-1β, but not il-6, is critical for the development of steady-state t(h)17 cells in the intestine
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280878/
https://www.ncbi.nlm.nih.gov/pubmed/22291094
http://dx.doi.org/10.1084/jem.20111703
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