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New insights into immune cell diversity in acute kidney injury

Cellular & Molecular Immunology volume 20, pages 680–682 (2023)Cite this article

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Acute kidney injury (AKI) is a frequent complication affecting hospitalized patients in medical wards and usually arises from ischemia‒reperfusion injury (IRI), sepsis, and nephrotoxic drugs. Excess infiltration and activation of immune cells in the kidney induce a continuous inflammatory response, which is characterized by substantial cytotoxicity that ultimately exacerbates kidney damage [1]. The role of individual immune cell types in AKI has been mostly investigated in previous years. However, despite the successful results in experimental studies, treatments targeting a broad immune response have yielded minor improvements in patient outcomes, in part due to the imprecise understanding of immune cell heterogeneity. Recently, the focus of AKI research has shifted toward gaining insight into the heterogeneity and dynamic changes in immune cells with novel experimental approaches such as single-cell analysis, thereby redefining AKI pathophysiology.

Neutrophils, which are primary effector cells of the innate immune system, become activated and are recruited to the kidneys during AKI; however, their mere presence does not necessarily indicate a causal role, given the inconsistent results of neutrophil blockade or depletion in various rodent studies. Neutrophils appear to function primarily as inflammatory indicators and amplifiers of AKI. These cells contribute substantially to kidney injury by obstructing the microvasculature and secreting toxic molecules, such as proteases, oxidants, cytokines, and neutrophil extracellular traps. To date, neutrophils have been viewed as a largely homogenous population. However, recent research has identified a novel Siglec-F-expressing subset of neutrophils that contributes to renal fibrosis in murine and human kidneys [2]. This study showed that the Ly-6G+ neutrophil population that coexpressed the eosinophil-specific surface marker Siglec-F was increased with kidney inflammation and fibrosis progression. Siglec-F+ neutrophils produce more profibrotic factors and collagen I than conventional neutrophils. TGF-β1 and GM-CSF may induce Siglec-F expression in neutrophils. Although this research focuses on the role of neutrophil subsets in chronic kidney disease (CKD), the findings suggest that specific neutrophil subsets can be generated by renal microenvironments and that different neutrophil subsets exhibit diverse biological functions. This may partially explain the inconsistent results from the aforementioned depletion studies. Because single-cell studies of neutrophils in kidney disease are still lacking, further investigation of neutrophil profiling in AKI is necessary.

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Acknowledgements

This study was supported by grants from the Shanghai Sailing Program (No: 20YF1423400 to B.D.), the National Natural Science Foundation of China (No: 81870462, 82070789 to F.D.; No: 82200747 to B.D.; No: 32002153 to S.W.), the Shanghai Huangpu Industry Support Grant (XK2020002 to F.D.), the Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education & Shanghai (CCTS-2022206 to F.D.), the Biomaterials & Regenerative Medicine Institute Cooperative Research Project (2022LHB01 to F.D.), the Clinical Research Program of 9th People’s Hospital (JYLJ202218 to F.D.), and the Postdoctoral Scientific Research Foundation of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (DengBo-2021-Scientific Research Start-up Funds to B.D.)

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  1. These authors contributed equally: Bo Deng, Sutian Wang.

Authors and Affiliations

  1. Division of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Bo Deng, Peihui Zhou & Feng Ding

  2. State Key Laboratory of Livestock and Poultry Breeding, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China

    Sutian Wang

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  1. Bo Deng
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BD and SW wrote the manuscript. PZ drew the picture. FD designed and performed the final proofreading of the manuscript.

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Correspondence to Feng Ding.

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Deng, B., Wang, S., Zhou, P. et al. New insights into immune cell diversity in acute kidney injury. Cell Mol Immunol 20, 680–682 (2023). https://doi.org/10.1038/s41423-023-01003-2

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