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Clec7a, primarily expressed on activated myeloid cells, functions as a pattern recognition receptor essential for regulating immune homeostasis. However, its specific effects and roles during AKI remain unclear. To investigate the role of Clec7a in AKI, we used a cisplatin\u2010induced acute kidney injury (cis\u2010AKI) model. We administered the Clec7a antagonist laminarin (LAM) and performed macrophage depletion. Additionally, we utilized siRNA to silence Clec7a and transferred Clec7a\u2010expressing primary peritoneal macrophages (PPMs) to mice to explore potential therapeutic targets. Chromatin immunoprecipitation (ChIP) assays were conducted to demonstrate the physical binding of NF\u2010\u03baB\/P65 to the Clec7a promoter. Our findings revealed an increase in Clec7a\u2010expressing macrophages in the cis\u2010AKI model. Blocking Clec7a signaling with LAM alleviated cisplatin\u2010induced renal inflammation, an effect also observed with the knockdown of Clec7a in transferred PPMs. Notably, this study shows that Clec7a activation by its agonist d\u2010Zymosan induces renal inflammation and up\u2010regulates iNOS in C57BL\/6 mice. Furthermore, both TLR4 and NF\u2010\u03baB inhibitors were able to antagonize LPS\u2010induced Clec7a expression. ChIP assays confirmed the physical binding of NF\u2010\u03baB to the Clec7a promoter, indicating the regulatory effect of the TLR4\/NF\u2010\u03baB signaling pathway on Clec7a expression. The synergistic signaling crosstalk between Clec7a\u2010Syk and TLR4\/NF\u2010\u03baB promotes and sustains the inflammatory phenotypes of M1 macrophages, contributing to damage in AKI. These findings provide novel insights into the pivotal role of Clec7a in renal inflammation and suggest its potential as a therapeutic target for AKI.<\/jats:p>","DOI":"10.1096\/fj.202504030rr","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T10:46:43Z","timestamp":1775645203000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Crosstalk Between Clec7a and\n                    <scp>TLR4<\/scp>\n                    Immune Pathway Drives Renal Damage in a Cisplatin\u2010Induced Acute Kidney Injury Model"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7233-6062","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Hematology The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyang","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pathology The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiping","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pathology The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9726-3186","authenticated-orcid":false,"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1053\/j.ajkd.2017.11.021","article-title":"Management of Acute Kidney Injury: Core Curriculum 2018","volume":"72","author":"Moore P. 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