Enhanced CBirl-specific Innate and Adaptive Immune Responses in Crohn's Disease

Background: CBirl is a dominant antigen with a role in innate and adaptive immunity in Mouse models of colitis and antibodies to CBirl are associated with severe human Crohn's disease (CD). Our aim was to determine whether CBirl stimulates innate and antigen-specific T-cell responses in CD. We demonstrate that CBirl enhanced IL-6 and IL-1 beta production by peripheral blood (PB) monocytes. Methods: Real time polymerase chain reaction (PCR) was used for measurement of IL6 and IL1 expression. [H-3] thymidine was used to measure T cell proliferation and Elispot assay was used to measure IFN gamma production. Results: IL-6 was significantly increased in monocytes from CD compared to controls and Ulcerative colitis (UC). Anti-CBirl(+) patients and IL-6 was inversely correlated. A significant increase in CBirl-specific peripheral T-cell proliferation was more evident in cells from CD than controls and UC. CBirl induced increased numbers of IFN-gamma(+) cells in lamina propria mononuclear cells (LPMC) from CD compared to UC and controls. Conclusions: CBirl includes enhanced peripheral innate and peripheral and mucosal antigen-specific T-cell responses in CD. Consistent with results from the Mouse, CBirl immune activation could play a role in CD.