Caspar Ohnmacht
,
Centre of Allergy & Environment (ZAUM), Technical University and Helmholtz Centre Munich, Munich, Germany
Joo-hong Park
,
Institut Pasteur, Paris, France
Sascha Cording
,
Institut Pasteur, Paris, France
James Wing
,
Immunology Frontier Research Center, Osaka University, Osaka, Japan
Koji Atarashi
,
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Yuuki Obata
,
The University of Tokyo, Tokyo, Canada
Valerie Gaboriau-Routhiau
,
INSERM 1163, Paris, France
Maria Fedoseeva
,
Centre of Allergy and Environment (ZAUM), Technical University and Helmholtz Centre Munich, Munich, Germany
Rute Marques
,
Institut Pasteur, Paris, France
Meinrad Busslinger
,
Research Institute of Molecular Pathology, Vienna, Austria
Nadine Cerf-Bensussan
,
INSERM, U989, and Institut IMAGINE, Université Paris Descartes-Sorbonne Paris Cité, Paris, France
David Voehringer
,
University Clinic Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
Koji Hase
,
The University of Tokyo, Tokyo, Japan
Kenya Honda
,
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Shimon Sakaguchi, M.D., Ph.D.
,
Immunology Frontier Research Center, Osaka University, Osaka, Japan
Gerard Eberl, PhD
,
Institut Pasteur, 75724 Paris, France
Alteration of the symbiotic microbiota early in life, or absence of it, leads to allergic pathologies. While it is unclear how microbiota regulates type 2 immunity, it is a strong inducer of pro-inflammatory Th17 cells and regulatory T cells (Tregs) in the intestine. We report that microbiota-induced Tregs express the nuclear hormone receptor RORγt, and differentiate along a pathway that also leads to Th17 cells and is regulated by the vitamin A metabolite retinoic acid. RORγt+ Tregs, and more generally RORγt+ T cells, inhibit the generation of Gata3+ T cells, which include Th2 cells and the other major population of intestinal, IL-33-responsive, Tregs. In the absence of RORγt+ Tregs, Th2-driven worm expulsion is more efficient while Th2-associated pathologies are exacerbated. Thus, microbiota regulates type 2 responses through the induction of “type 3” RORγt+ Tregs and Th17 cells, and acts as a key factor in balancing immune responses at mucosal surfaces.
