Geem Duke, Harusato Akihito, Flannigan Kyle, Denning Timothy L
*Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia; and †Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.
Inflamm Bowel Dis. 2015 Jun;21(6):1409-18. doi: 10.1097/MIB.0000000000000343.
Regulatory CD4 T (Treg) cells are comprised of a heterogeneous population of cells that play a vital role in suppressing inflammation and maintaining immune tolerance. The immunoregulatory function of Treg cells is especially important in the intestine where the mucosa is exposed to a diverse array of foreign antigens-including those derived from food and commensal bacteria. Treg cells are enriched in the intestinal lamina propria and provide a crucial function in promoting tolerance to enteric antigens while modulating tissue inflammation. Correspondingly, Treg cell dysfunction is associated with a breakdown in intestinal tolerance and the induction of aberrant immune responses that may contribute to the pathogenesis of inflammatory bowel disease. This review will provide a brief overview of Treg cell biology with a focus on Foxp3 Treg and type 1 regulatory (Tr1) cells and summarize the evidence for defective Treg cells in experimental and human inflammatory bowel disease. The potential application of Treg cells as a treatment for inflammatory bowel disease will also be discussed in the context of Treg infusion therapy and the in vivo induction/expansion of intestinal Treg cells.
调节性CD4 T(Treg)细胞由异质性细胞群体组成,在抑制炎症和维持免疫耐受中发挥着至关重要的作用。Treg细胞的免疫调节功能在肠道中尤为重要,因为肠道黏膜会接触到各种各样的外来抗原,包括来自食物和共生细菌的抗原。Treg细胞在肠道固有层中富集,在促进对肠道抗原的耐受性同时调节组织炎症方面发挥着关键作用。相应地,Treg细胞功能障碍与肠道耐受性的破坏以及异常免疫反应的诱导有关,这可能导致炎症性肠病的发病机制。本综述将简要概述Treg细胞生物学,重点关注Foxp3 Treg和1型调节性(Tr1)细胞,并总结实验性和人类炎症性肠病中Treg细胞缺陷的证据。还将在Treg输注疗法以及肠道Treg细胞的体内诱导/扩增的背景下讨论Treg细胞作为炎症性肠病治疗方法的潜在应用。