Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Mucosal Immunol. 2019 Jan;12(1):21-35. doi: 10.1038/s41385-018-0113-5. Epub 2018 Nov 29.
The small intestinal and colonic lamina propria are populated with forkhead box P3 (FOXP3)CD4 regulatory T cells (Tregs) and interleukin-10-producing T cells that orchestrate intestinal tolerance to harmless microbial and food antigens. Expression of co-inhibitory receptors such as CTLA-4 and PD-1 serve as checkpoints to these cells controlling their T-cell receptor (TCR)-mediated and CD28-mediated activation and modulating the phenotype of neighboring antigen presenting cells. Recent discoveries on the diversity of co-inhibitory receptors and their selective cellular expression has shed new light on their tissue-dependent function. In this review, we provide an overview of the co-inhibitory pathways and checkpoints of Treg and effector T cells and their mechanisms of action in intestinal homeostasis. Better understanding of these inhibitory checkpoints is desired as their blockade harbors clinical potential for the treatment of cancer and their stimulation may offer new opportunities to treat chronic intestinal inflammation such as inflammatory bowel disease.
小肠和结肠固有层中存在叉头框 P3（FOXP3）+ CD4 调节性 T 细胞（Treg）和白细胞介素-10 产生 T 细胞，它们协调肠道对无害微生物和食物抗原的耐受。共抑制受体（如 CTLA-4 和 PD-1）的表达作为这些细胞的检查点，控制其 T 细胞受体（TCR）介导和 CD28 介导的激活，并调节邻近抗原呈递细胞的表型。最近对共抑制受体的多样性及其选择性细胞表达的发现，为它们的组织依赖性功能提供了新的认识。在这篇综述中，我们概述了 Treg 和效应 T 细胞的共抑制途径和检查点及其在肠道稳态中的作用机制。更好地了解这些抑制检查点是可取的，因为它们的阻断具有治疗癌症的临床潜力，而它们的刺激可能为治疗慢性肠道炎症（如炎症性肠病）提供新的机会。
