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.

中文翻译：

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打破平衡：肠道稳态中的抑制性检查点。

小肠和结肠固有层充满叉头盒 P3 (FOXP3) ⁺ CD4 ⁺调节性 T 细胞 (Tregs) 和产生白介素 10 的 T 细胞协调肠道对无害微生物和食物抗原的耐受性。CTLA-4 和 PD-1 等共抑制受体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。最近关于共抑制受体多样性及其选择性细胞表达的发现为了解它们的组织依赖性功能提供了新的思路。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，以及它们在肠道稳态中的作用机制。