Innate lymphoid cells (ILCs) are lymphocytes that regulate immune responses. Little is known about these cells in the kidney. New findings now reveal a role for group 3 ILCs (ILC3s) in regulating kidney fibrosis, following their migration from the intestine via a CXCR6–CXCL16 signalling axis.

Using single-cell RNA sequencing of genetic models combined with structural predictions of molecular interactions, the researchers demonstrated that PD-1, expressed by newly migrated ILC3s, enhances the production of IL-17A (an ILC3 effector cytokine), which promotes kidney fibroblast activation to induce fibrosis. Mechanistically, expression of PD-1 by ILC3s impedes the endocytosis of IL-23R by binding competitively to it. The resulting surface expression of IL-23R enables IL-23-induced signalling through the JAK2–STAT3–RORγt pathway to induce IL-17A release.

先天淋巴细胞 (ILC) 是调节免疫反应的淋巴细胞。人们对肾脏中的这些细胞知之甚少。现在的新发现揭示了第 3 组 ILC (ILC3) 通过 CXCR6-CXCL16 信号轴从肠道迁移后在调节肾纤维化中的作用。

利用遗传模型的单细胞 RNA 测序结合分子相互作用的结构预测，研究人员证明，新迁移的 ILC3 表达的 PD-1 可以增强 IL-17A（一种 ILC3 效应细胞因子）的产生，从而促进肾成纤维细胞活化以诱发纤维化。从机制上讲，ILC3 表达的 PD-1 通过与 IL-23R 竞争性结合来阻碍 IL-23R 的内吞作用。由此产生的 IL-23R 表面表达使 IL-23 能够通过 JAK2-STAT3-RORγt 途径诱导信号传导，从而诱导 IL-17A 释放。