TGF-β1 reduces the differentiation of porcine IgA-producing plasma cells by inducing IgM B cells apoptosis via Bax/Bcl2-Caspase3 pathway.

FASEB J

State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

Published: October 2023

Transforming growth factor β1 (TGF-β1) performs a critical role in maintaining homeostasis of intestinal mucosa regulation and controls the survival, proliferation, and differentiation of many immune cells. In this study, we discovered that the infection of porcine epidemic diarrhea virus (PEDV), a coronavirus, upregulated TGF-β1 expression via activating Tregs. Besides, recombinant porcine TGF-β1 decreased the percentage of CD21 B cells within the lymphocyte population in vitro. We further found that TGF-β1 reduced the IgA-secreting B cell numbers and also inhibited plasma cell differentiation. Additional investigations revealed that TGF-β1 induced the apoptosis of IgM B cells in both peyer's patches (PPs) and peripheral blood (PB) through the activation of the Bax/Bcl2-Caspase3 pathway. Conversely, the application of the TGF-β1 signaling inhibitor SB431542 significantly antagonized the TGF-β1-induced reduction of IgA secretion and B cell apoptosis and restored plasma cell differentiation. Collectively, TGF-β1 plays an important role in regulating the survival and differentiation of porcine IgA-secreting B cells through the classical mitochondrial apoptosis pathway. These findings will facilitate future mucosal vaccine designs that target the regulation of TGF-β1 for the control of enteric pathogens in the pig industry.

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Source
http://dx.doi.org/10.1096/fj.202300824RRDOI Listing

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