Endoplasmic reticulum-associated degradation and beyond: The multitasking roles for HRD1 in immune regulation and autoimmunity.

Endoplasmic reticulum-associated degradation and beyond: The multitasking roles for HRD1 in immune regulation and autoimmunity. J Autoimmun. 2020 Feb 10;:102423 Authors: Xu Y, Fang D Abstract Endoplasmic reticulum (ER)-associated degradation (ERAD) is a mechanism against ER stress, wherein unfolded/misfolded proteins accumulated in the ER are transported to the cytosol for degradation by the ubiquitin-proteasome system. The ER resident E3 ubiquitin ligase HRD1 has been identified as a key ERAD factor that directly catalyzes ubiquitin conjugation onto the unfolded or misfolded proteins for proteasomal degradation. The abnormally increased HRD1 expression was discovered in rheumatoid synovial cells, providing the first evidence for HRD1 dysregulation involved in human inflammatory pathogenesis. Further studies shown that inflammatory cytokines involved in rheumatoid pathogenesis including IL-1β, TNF-α, IL-17 and IL-26 induce HRD1 expression. Recent studies using mice with tissue-specific targeted deletion of HRD1 gene have revealed important functions of HRD1 in immune regulation and inflammatory diseases. HRD1 has been shown critical for dendritic cell expression of antigens to both CD4 and CD8 T cells. Both TCR and costimulatory receptor CD28 signaling induces HRD1 expression, which promotes T cell clonal expansion and IL-2 production. Together with the fact that HRD1 is required for maintaining the stability of regulatory T cell (Treg) stabil...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research

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