The microbiota regulates type 2 immunity through RORγt<sup>+</sup> T cells

Caspar Ohnmacht, Joo Hong Park, Sascha Cording, James B. Wing, Koji Atarashi, Yuuki Obata, Valérie Gaboriau-Routhiau, Rute Marques, Sophie Dulauroy, Maria Fedoseeva, Meinrad Busslinger, Nadine Cerf-Bensussan, Ivo G. Boneca, David Voehringer, Kouji Hase, Kenya Honda, Shimon Sakaguchi, Gérard Eberl

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326 Citations (Scopus)

Abstract

Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (T<inf>H</inf>17) cells and regulatory T cells (T<inf>regs</inf>) in the intestine. Here, we report that microbiota-induced T<inf>regs</inf> express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to T<inf>H</inf>17 cells. In the absence of RORγt<sup>+</sup> T<inf>regs</inf>, T<inf>H</inf>2-driven defense against helminths is more efficient, whereas T<inf>H</inf>2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt<sup>+</sup> T<inf>regs</inf> and T<inf>H</inf>17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.

Original languageEnglish
Pages (from-to)989-993
Number of pages5
JournalScience
Volume349
Issue number6251
DOIs
Publication statusPublished - 2015 Aug 28
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Ohnmacht, C., Park, J. H., Cording, S., Wing, J. B., Atarashi, K., Obata, Y., Gaboriau-Routhiau, V., Marques, R., Dulauroy, S., Fedoseeva, M., Busslinger, M., Cerf-Bensussan, N., Boneca, I. G., Voehringer, D., Hase, K., Honda, K., Sakaguchi, S., & Eberl, G. (2015). The microbiota regulates type 2 immunity through RORγt<sup>+</sup> T cells. Science, 349(6251), 989-993. https://doi.org/10.1126/science.aac4263