Single-cell RNA sequencing identifies a proinflammatory S100a8/a9⁺ macrophage subset contributing to acute kidney injury.

Authors

Ting Ren, Xinni Zhang, Jinghan Feng, Xiaoyan Wang, Zhouping Zou, Qi Zeng, Fangyuan Peng, Qiang Yang, Xiaoqiang Ding, Ping Jia

Published in

Inflammation research : official journal of the European Histamine Research Society ... [et al.]. Volume 75. Issue 1. Oct 17, 2026. Epub Oct 17, 2026.

Abstract

Macrophages represent a heterogeneous cell population in the kidney. However, macrophage subsets and their role in endotoxemia-induced acute kidney injury (AKI) remain elucidated.
Single-cell RNA sequencing was performed to identify macrophage subpopulations in mouse kidney following lipopolysaccharide (LPS) challenge. AKI was induced by LPS treatment or renal ischemia reperfusion injury in wild-type or S100a9^-/- mice. Silencing or overexpression of S100a9 was carried out to assess its function and contribution to LPS-induced inflammation and AKI. In addition, bone marrow cells from S100a9^-/- mice were injected into the recipient mice to determine the effect of S100a9 deletion in macrophage differentiation and renal inflammatory injury.
By using single-cell RNA sequencing, we identified a unique S100a8/a9⁺Ly6c^high proinflammatory macrophage subpopulation in mouse kidney following LPS challenge. LPS administration induced the infiltration of Ly6c⁺ macrophages into kidney tissues and significantly upregulated the expression of S100a8 and S100a9. S100a9 deletion downregulated S100a8 expression, decreased CD11b⁺Ly6c^high macrophages, and suppressed proinflammatory cytokine production in the kidney, attenuating LPS or ischemia reperfusion-induced renal inflammation and AKI. Bone marrow transplantation from S100a9^-/- mice donors, but not from wild-type mice donors, reduced infiltration of CD11b⁺Ly6c^high macrophages and renal inflammatory injury. S100a8/a9 overexpression activated the nuclear factor-κB signaling pathway and promoted the production of proinflammatory cytokines in macrophages.
S100a8/a9 plays a regulatory role in CD11b⁺Ly6c^high macrophage population differentiation, contributing to endotoxemia-induced AKI. S100a8/a9 blockade may be a novel therapeutic strategy for the prevention or attenuation of AKI.

PMID:
42892624
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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