CCL17型
中央控制室4
医学
CCL22型
趋化因子
免疫学
趋化因子受体
肾小球肾炎
肾
免疫系统
内科学
作者
Ning Song,Hans‐Joachim Paust,Nariaki Asada,Anett Peters,Anna Kaffke,Christian Krebs,Ulf Panzer,Jan-Hendrik Riedel
出处
期刊:American Journal of Nephrology
[S. Karger AG]
日期:2023-09-23
卷期号:: 1-11
摘要
The chemokine receptor CCR4 is expressed by divers CD4+ T cell subsets including regulatory T cells (Tregs) but its functional importance for leukocyte recruitment and the relevance of its two corresponding chemokines CCL17 and CCL22 have not been studied in immune mediated crescentic glomerulonephritis (cGN).Utilizing the single cell RNA sequencing (scRNAseq) data in analyzing leukocytes isolated from both human and murine nephritic kidneys we identified CCL17 as a potential therapeutic target in immune mediated renal disease. Using a mouse model of murine cGN we then delineated the effects of targeting CCL17 by neutralizing antibodies and in Ccl17 gene-deficient mice.Unsupervised scRNAseq analyses identified the CCL17-CCR4 axis as a mechanism potentially involved in renal T cell migration. Analyses of functional kidney impairment and histopathological kidney damage revealed an attenuation of crescentic GN in anti-CCL17 antibody-treated mice which was corroborated using in Ccl17 gene-deficient mice. Immunohistochemical analyses revealed that these changes were accompanied by an affected renal Treg recruitment in both experimental approaches.The chemokine receptor CCR4 and its corresponding chemokine CCL17 are expressed in human and murine cGN and targeting the CCR4-CCL17 axis by neutralizing antibodies as well as Ccl17 gene-deficiency led to increased renal Treg recruitment and reduced histological and functional kidney damage in murine crescentic glomerulonephritis.
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