Anti-CD45RB antibody therapy attenuates renal ischemia-reperfusion injury by inducing regulatory B cells

Taishi Fang, Tai Yeon Koo, Jae Ghi Lee, Joon Young Jang, Yixuan Xu, Ju Hee Hwang, Sunjoo Park, Ji Jing Yan, Jung Hwa Ryu, Yeon Mi Ryu, Sang Yeob Kim, Kyung Suk Suh, Jaeseok Yang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background Regulatory B cells are a newly discovered B cell subset that suppresses immune responses. Recent studies found that both anti-CD45RB and anti-Tim-1 treatments regulate immune responses by inducing regulatory B cells; however, the role of these cells in renal ischemia-reperfusion injury (IRI) is unknown. Methods Usingmouse models, including T cell-deficient (RAG1 knockout and TCRa knockout)mice and B cell-deficient (mMT)mice, we investigated the effects of regulatory B cells and anti-CD45RB on IRI and the mechanisms underlying these effects. Results Adoptive transfer of regulatory B cells before or after IRI attenuated renal IRI. Anti-CD45RB treatment with or without anti-Tim-1 before IRI increased renal infiltration of CD19+Tim-1+ regulatory B and regulatory T cells. Anti-CD45RB decreased serum creatinine levels, pathologic injury score, tubular apoptosis, and proinflammatory cytokines levels, whereas IL-10 levels increased. Following IRI, anti-CD45RB with or without anti-Tim-1 also induced regulatory B cells, improving renal function and tubular regeneration. In RAG1 knockout mice with B cell transfer, TCRα knockout mice, and wild-type mice with T cell depletion, anti-CD45RB increased regulatory B cells and attenuated IRI. However, anti-CD45RB did not attenuate IRI in RAG1 knockout mice with T cell transfer or μMT mice and induced only mild improvement inwild-typemicewith B cell depletion. Furthermore, B cell-deficientmice receiving B cells fromIL-10 knockout mice (but not from wild-type mice) did not show renal protection against IRI when treated with anti-CD45RB. Conclusions Anti-CD45RB treatment attenuated acute renal injury and facilitated renal recovery after IRI through induction of IL-10+ regulatory B cells, pointing to anti-CD45RB as a potential therapeutic strategy in renal IRI.

Original languageEnglish
Pages (from-to)1870-1885
Number of pages16
JournalJournal of the American Society of Nephrology
Volume30
Issue number10
DOIs
StatePublished - 2019

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