Attenuation of TNF-driven murine ileitis by intestinal expression of the viral immunomodulator CrmD

Tumor necrosis factor alpha (TNF alpha) is a key pathogenic factor in Crohn's disease and rheumatoid arthritis. TNF Delta ARE mice express high levels of TNF alpha and present Crohn's-like ileitis and arthritis. Alterations in the chemokine network could underline the TNF-driven ileitis. The aim of this study was to evaluate the role of TNF and chemokines in ileitis using ectromelia virus cytokine response modifier D (CrmD), a protein that binds TNF alpha and a limited number of chemokines. We generated transgenic mice expressing CrmD in intestinal epithelial cells (vCrmD mice) and crossed them with the TNF Delta ARE mice to test whether CrmD could affect TNF-driven inflammatory processes. During homeostasis, only the number of B cells in the lamina propria was reduced by CrmD expression. Interestingly, CrmD expression in the intestine markedly attenuated the inflammatory infiltrates in the ileum of TNF Delta ARE mice, but did not affect development of arthritis. Our results suggest that CrmD affects development of ileitis by locally affecting both TNF and chemokine function in the ileum.