Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cells

Antigen presentation via major histocompatibility complex (MHC) class I and II receptors plays a fundamental role in T cell-mediated adaptive immunity. A dysregulation of this fine-tuned recognition might result the development autoimmune diseases such as inflammatory bowel that are characterized by chronic relapsing inflammation intestinal tract damaged epithelial barrier. While MHCII usually expressed professional antigen presenting cells (APC) only, there is increasing evidence non-immune (IEC) express upon stimulation with IFN-γ thus act non-professional APC. However, little known about other factors regulating MHC expression. Here, we identify IL-27 an inducer different MHCI receptor subtypes invariant chain (CD74/li) IEC STAT1/IRF1/CIITA axis. CIITA, MHCII, CD74 expression was significantly increased from Crohn’s disease (CD) patients active compared to controls or CD remission. phagocytosed digested external antigens apoptotic cells. strongly stimulated processing immunoproteasome IRF1-dependent manner. In co-culture experiments, antigen-primed enhanced lymphocyte proliferation IL-2 secretion, dependent on direct cell-cell contact. pretreatment CD4 + cell reduced levels lymphocytes coculture. summary, identified novel regulator receptors, underscoring importance