Immune regulation of the unfolded protein response at the mucosal barrier in viral infection

Wang, Ran; Moniruzzaman, Md.; Shuffle, Eric; Lourie, Rohan; Hasnain, Sumaira Z

mucosal barrier regeneration and renewed homeostasis. IL-10 is an example of the multifaceted role a single cytokine can have on viral infection and the UPR. IL-10 suppresses B-cell antibody responses and T-cell immunity; thus, its neutralisation leads to viral clearance. 79 Human cytomegalovirus has been found to encode a decoy IL-10-like cytokine, which signals through the human IL-10 receptor to circumvent detection and destruction by the host immune system. 80 We have demonstrated that IL-10 suppresses the UPR in secretory goblet cells in the intestine, 54 allowing for increased protein production. Therefore, along with IL-10-mediated immunosuppressive effects on the immune cells, IL-10-induced protein production (via the regulation of the UPR) would allow for increased viral replication in these highly productive secretory cells. Despite the negative effects of IL-10 in acute viral infection, the importance of IL-10 in attenuating chronic inflammation is unequivocal. 81, 82 Regardless, these cytokines controlling secretory protein synthesis in nonimmune cells are an overlooked paradigm in immunity. More detailed understanding will help identify novel targets that can be modulated in acute infection and more broadly in chronic inflammatory diseases to alleviate tissue damage.