Science (New York, N.Y.) · 2019
Epithelial endoplasmic reticulum stress orchestrates a protective IgA response.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Grootjans Joep, Krupka Niklas, Hosomi Shuhei, Matute Juan D, Hanley Thomas, Saveljeva Svetlana, Gensollen Thomas, Heijmans Jarom, Li Hai, Limenitakis Julien P, Ganal-Vonarburg Stephanie C, Suo Shengbao, Luoma Adrienne M, Shimodaira Yosuke, Duan Jinzhi, Shih David Q, Conner Margaret E, Glickman Jonathan N, Fuhler Gwenny M, Palm Noah W, de Zoete Marcel R, van der Woude C Janneke, Yuan Guo-Cheng, Wucherpfennig Kai W, Targan Stephan R, Rosenstiel Philip, Flavell Richard A, McCoy Kathy D, Macpherson Andrew J, Kaser Arthur, Blumberg Richard S
Аннотация
Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.