The microbiota regulates type 2 immunity through RORgt+ T cells (Science 2015, 349(6251):989-993)

報告日期: 2016/11/29
報告時間: 5:10/6:00
報告學生: 陳佩琪
講評老師: 何漣漪
附件下載: 下載[1605-1473728510-1.pdf] 

The microbiota regulates type 2 immunity through RORγt+ 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, Koji Hase, Kenya Honda, Shimon Sakaguchi, Gérard Eberl,Science (2015) 349:989-993.

Speaker: Pei-Chi Chen (陳佩琪)                   Time : 17:10~18:00, Nov.29, 2016

Commentator: Dr. Lien-I, Hor (何漣漪)        Place: Room 602

The intestinal microbiotas affect various physiological functions in human through modulation of host’s immune system. In turn, it is well established that bacterial signals shape intestinal homeostasis through regulating the development of T helper 17 (TH17) cells and regulatory T (Treg) cells [1]. However, the detail mechanism of how microbiotas regulate mucosal immunity remains unknown. In this study,Ohnmacht et al. found that there are two major types of Treg cells in the colon lamina propria─RORγt+ Tregs and GATA3+Tregs. Only the development of RORγt+ Tregs, but not GATA3+Tregs could be regulated by intestinal microbiota. Indeed, a combination of 17 Clostridia species, segmented filamentous bacteria (SFB), and SCFA butyrate efficiently induced the generation of RORγt+Tregs in the colon. The induction of RORγt+ Tregs also induced by oral antigen that dependent on DCs and MHC II presenting. Furthermore, the authors also showed that the differentiation of RORγt+ Tregs and TH17s followed the similar pathway, but the vitamin A metabolite retinoic acid (RA) promoted the development of RORγt+ Tregs rather than TH17s. In addition, the authors took the next step to investigate the function of RORγt+ Tregs. They found that Foxp3Cre x Rorc(γt)FL mice, RORγt+ Tregs conditional knockout mice, expressed more frequencies of GATA3+ Tregs and GATA3+ TH2 cells than WT mice. Besides, mice that lack RORγt+ Tregs developed a more severe of oxazolone-induced colitis, a TH2 dependent colitis model, and more resistant to infection of helminthes. In the end of study, the authors reported that RORγt+ Tregs controlled type 2 immunity through both cell-intrinsic (interferon regulatory factor 4, IRF4 dependent) and cell-extrinsic (cytotoxic T-lymphocyte-associated protein 4, CTLA4, dependent) mechanisms. In conclusion, the microbiota regulates type 2 immunity through RORγt+ T cells and plays a critical role in balancing the mucosal immune response [2].

 

References

  1. Honda K, Littman DR, The microbiota in adaptive immune homeostasis and disease. Nature, 535:75-84 (2016).
  2. Hegazy AN, Powrie F, Microbiota RORgulates intestinal suppressor T cells. Science, 349: 929–930 (2015).