Molecules and Cells

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Fig. 4.

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Fig. 4. (A) Roles of the UPR in secretory cells; the UPR regulates ER expansion and protein secretion, and is therefore essential for development, differentiation, and specialized functions of highly secretory cells, such as pancreatic β cells, exocrine acinar cells, hepatocytes, and salivary gland epithelial cells. (B) Roles of the UPR in immune cells; the UPR plays crucial roles in the development of immune cells, such as plasma cells, DCs, and eosinophils. ER stress also regulates immune cell differentiation, activation, and cytokine expression. In CD4+ T cells, the UPR regulates differentiation to Th2 cells, Th17 cells, and Tregs, and has an important function in TCR-mediated activation. The IRE1–XBP1 pathway is important for differentiation of CD8+ T cells into effector cells. The UPR is also activated during B cell differentiation, and XBP1s is essential for antibody secretion from plasma cells. ER stress strongly influences innate and adaptive immune responses by modulating the production of pro-inflammatory cytokines in B cells, macrophages, and DCs. In macrophages, XBP1s and ATF6 function as positive regulators of inflammatory cytokine expression following TLR stimulation. XBP1s also regulates developmental and inflammatory responses of DCs. However, in DCs of tumor microenvironments, XBP1s induces abnormal lipid accumulation and inhibits anti-tumor immunity. TCR, T cell receptor; Th2, T helper type 2; Tregs, regulatory T cells; TLR, Toll-like receptor.
Mol. Cells 2018;41:705~716
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