Maurice Müller Laboratories (DKF), Universitätsklinik für Viszerale Chirurgie und Medizin Inselspital, Murtenstrasse 35, University of Bern, Bern, Switzerland.
Immunity. 2011 May 27;34(5):794-806. doi: 10.1016/j.immuni.2011.03.021. Epub 2011 May 19.
Mammals harbor a dense commensal microbiota in the colon. Regulatory T (Treg) cells are known to limit microbe-triggered intestinal inflammation and the CD4+ T cell compartment is shaped by the presence of particular microbes or bacterial compounds. It is, however, difficult to distinguish whether these effects reflect true mutualistic immune adaptation to intestinal colonization or rather idiosyncratic immune responses. To investigate truly mutualistic CD4+ T cell adaptation, we used the altered Schaedler flora (ASF). Intestinal colonization resulted in activation and de novo generation of colonic Treg cells. Failure to activate Treg cells resulted in the induction of T helper 17 (Th17) and Th1 cell responses, which was reversed by wild-type Treg cells. Efficient Treg cell induction was also required to maintain intestinal homeostasis upon dextran sulfate sodium-mediated damage in the colon. Thus, microbiota colonization-induced Treg cell responses are a fundamental intrinsic mechanism to induce and maintain host-intestinal microbial T cell mutualism.
哺乳动物的结肠中栖息着密集的共生微生物菌群。众所周知，调节性 T（Treg）细胞可以限制微生物引发的肠道炎症，而 CD4+T 细胞群的形成则受到特定微生物或细菌化合物的影响。然而，很难区分这些影响是反映了对肠道定植的真正共生免疫适应性，还是反映了特有的免疫反应。为了研究真正的共生 CD4+T 细胞适应性，我们使用了改变的 Schaedler 菌群（ASF）。肠道定植导致结肠 Treg 细胞的激活和新生。如果 Treg 细胞不能被激活，就会导致辅助性 T 细胞 17（Th17）和 Th1 细胞反应的诱导，而野生型 Treg 细胞可以逆转这种反应。在葡聚糖硫酸钠介导的结肠损伤后，为了维持肠道内稳态，也需要有效的 Treg 细胞诱导。因此，菌群定植诱导的 Treg 细胞反应是诱导和维持宿主-肠道微生物 T 细胞共生的基本内在机制。
