B Lymphocyte-Derived CCL7 Augments Neutrophil and Monocyte Recruitment, Exacerbating Acute Kidney Injury.
Journal of immunology (Baltimore, Md. : 1950)
American Association of Immunologists
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Inaba, A., Tuong, Z., Riding, A. M., Mathews, R. J., Martin, J. L., Saeb-Parsy, K., & Clatworthy, M. (2020). B Lymphocyte-Derived CCL7 Augments Neutrophil and Monocyte Recruitment, Exacerbating Acute Kidney Injury.. Journal of immunology (Baltimore, Md. : 1950), 205 (5), 1376-1384. https://doi.org/10.4049/jimmunol.2000454
Acute kidney injury (AKI) is a serious condition affecting a fifth of hospital in-patients. B lymphocytes have immunological functions beyond antibody production and may produce cytokines and chemokines which modulate inflammation. Here we investigated leucocyte responses in a mouse models of AKI and observed an increase in circulating and kidney B cells, particularly a B220low subset, following AKI. We found that B cells produce the chemokine CCL7, with the potential to facilitate neutrophil and monocyte recruitment to the injured kidney. Siglec-G-deficient mice, which have increased numbers of B220low innate B cells and a lower B cell activation threshold, had increased Ccl7 transcripts, neutrophil and monocyte numbers in the kidney and more severe AKI. CCL7 blockade in mice reduced myeloid cell infiltration into the kidney and ameliorated AKI. In two independent cohorts of human patients with AKI, we observed significantly higher CCL7 transcripts compared to controls, and in a third cohort, an increase in urinary CCL7 levels in AKI, supporting the clinical importance of this pathway. Together our data suggest that B cells contribute to early sterile inflammation in AKI via the production of leucocyte-recruiting chemokines.
Medical Research Council National Institute of Health Research Wellcome Trust Versus Arthritis Cure Challenge Research Grant
MEDICAL RESEARCH COUNCIL (MR/M003868/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC)
Arthritis Research UK (21777)
Embargo Lift Date
External DOI: https://doi.org/10.4049/jimmunol.2000454
This record's URL: https://www.repository.cam.ac.uk/handle/1810/308289
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