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논문분류	춘계학술대회 초록집
제목	Anti-CD45RB antibody therapy attenuates renal ischemia-reperfusion injury by inducing regulatory B cells
저자	Sun-Kyung Lee, Taishi Fang, Tai Yeon Koo, Jae-Ghi Lee, Joon Young Jang, Ju Hee Hwang, Ji-Jing Yan, Jung-Hwa Ryu, Kyung-Suk Suh, Jaeseok Yang
출판정보	2019; 2019(1):
키워드	acute renal injury \| ischemia-reperfusion injury \| regulatory B cell
초록	Regulatory B cells (Bregs) are a new B cell subset that suppresses immune responses. Recently, both anti-CD45RB and anti-Tim-1 treatments have been found to regulate immune responses by inducing Bregs; however, the role of Bregs in renal ischemia-reperfusion injury (IRI) has not been shown. We investigated impacts of Bregs and anti-CD45RB on IRI and its mechanisms using mouse models of bilateral renal IRI. Adoptive transfer of Bregs prior to or following IRI attenuated renal IRI. Anti-CD45RB treatment with or without anti-Tim-1 prior to IRI increased the renal infiltration of CD19+Tim-1+ Bregs and regulatory T cells. Anti-CD45RB decreased serum creatinine levels, pathologic injury score, and tubular apoptosis. Levels of IL-1β, IL-6, MCP-1, IFN-γ, and IL-17 were decreased, whereas IL-10 was increased in the CD45RB group. Following IRI, anti-CD45RB with or without anti-Tim-1 also induced Bregs, thereby 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 Bregs 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 in wild-type mice with B cell depletion. Furthermore, B cells from IL-10 knockout mice did not show anti-CD45RB-mediated renal protection against IRI, in contrast to those from wild-type mice. Anti-CD45RB treatment attenuated acute renal injury and facilitated renal recovery after IRI through induction of IL-10+ Bregs. The present study suggests anti-CD45RB as a potential therapeutic strategy in renal IRI.
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