Group2 innate lymphoid cells ameliorate renal fibrosis and dysfunction associated with adenine-induced CKD

IF 3.7 4区医学 Q2 CELL BIOLOGY

Cellular immunology Pub Date : 2024-05-12 DOI:10.1016/j.cellimm.2024.104828

Ryuichi Nagashima , Hiroki Ishikawa , Yoshihiro Kuno , Chikara Kohda , Koji Eshima , Masayuki Iyoda

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Abstract

Renal fibrosis is a common pathway of chronic kidney disease (CKD) progression involving primary kidney injury and kidney diseases. Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses irrespective of antigen presentation and play a reno-protective role in kidney injury and disease. In the present study, we observed a decrease in kidney-resident ILC2s in CKD and found that enrichment of ILC2s in the kidney ameliorates renal fibrosis. In CKD kidney, ILC2s preferentially produced IL-13 over IL-5 in response to IL-33 stimulation, regardless of ST2L expression. Moreover, GATA3 expression was decreased in ILC2s, and T-bet+ ILC1s and RORγt+ ILC3s were increased in CKD kidney. Adoptive transfer of kidney ILC2s into adenine-induced CKD model mouse improved renal function and fibrosis. Renal fibroblasts cultured with IL33-activated kidney ILC2s suppressed myofibroblast trans-differentiation through Acta2 and Fn-1 regulation. These results suggest that kidney ILC2s prevent CKD progression via improvement of renal fibrosis. Our findings also suggest that ILC2s may contribute to the development of new therapeutic agents and strategies for tissue fibroses.

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第 2 组先天性淋巴细胞可改善与腺嘌呤诱导的慢性肾脏病相关的肾脏纤维化和功能障碍

肾脏纤维化是慢性肾脏病（CKD）进展的常见途径，涉及原发性肾损伤和肾脏疾病。第 2 组先天性淋巴细胞（ILC2s）介导第 2 型免疫反应，与抗原呈递无关，并在肾损伤和肾脏疾病中发挥肾保护作用。在本研究中，我们观察到 CKD 肾脏驻留的 ILC2 减少，并发现 ILC2 在肾脏中的富集可改善肾脏纤维化。在 CKD 肾脏中，ILC2s 在 IL-33 刺激下优先产生 IL-13 而不是 IL-5，与 ST2L 表达无关。此外，在CKD肾脏中，ILC2s的GATA3表达减少，T-bet+ ILC1s和RORγt+ ILC3s增加。将肾脏 ILC2s 移植到腺嘌呤诱导的 CKD 模型小鼠体内可改善肾功能和肾纤维化。用IL33激活的肾脏ILC2培养的肾脏成纤维细胞通过Acta2和Fn-1的调控抑制了肌成纤维细胞的转分化。这些结果表明，肾脏 ILC2 可通过改善肾脏纤维化来预防 CKD 的进展。我们的研究结果还表明，ILC2s 可能有助于开发治疗组织纤维化的新药和新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular immunology 生物-免疫学

CiteScore

8.20

自引率

2.30%

发文量

102

审稿时长

30 days

期刊介绍： Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.