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B Lymphocyte-Derived CCL7 Augments Neutrophil and Monocyte Recruitment, Exacerbating Acute Kidney Injury.

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Tuong, Zewen K 
Riding, Alexandra M  ORCID logo
Mathews, Rebeccah J  ORCID logo


Acute kidney injury (AKI) is a serious condition affecting one fifth of hospital inpatients. B lymphocytes have immunological functions beyond Ab production and may produce cytokines and chemokines that modulate inflammation. In this study, we investigated leukocyte responses in a mouse model 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, increased 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 with controls, and in a third cohort, we observed 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 leukocyte-recruiting chemokines.



Acute Kidney Injury, Animals, B-Lymphocytes, Chemokine CCL7, Cytokines, Disease Models, Animal, Female, Humans, Inflammation, Kidney, Leukocytes, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Monocytes, Neutrophils

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J Immunol

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The American Association of Immunologists
Medical Research Council (MR/M003868/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC)
Arthritis Research UK (21777)
Wellcome Trust (200110/Z/15/Z)
Medical Research Council (MR/N024907/1)
Medical Research Council (MR/S035842/1)
Medical Research Council National Institute of Health Research Wellcome Trust Versus Arthritis Cure Challenge Research Grant