The Cd200 Regulates Inflammation In Mice Independently Of Tnf-Alpha Production

Inflammatory bowel disease is characterized by the infiltration of immune cells and chronic inflammation. The immune inhibitory receptor, CD200R, is involved in the downregulation of the activation of immune cells to prevent excessive inflammation. We aimed to define the role of CD200R ligand-CD200 in the experimental model of intestinal inflammation in conventionally-reared mice. Mice were given a dextran sodium sulfate solution in drinking water. Bodyweight loss was monitored daily and the disease activity index was calculated, and a histological evaluation of the colon was performed. TNF-alpha production was measured in the culture of small fragments of the distal colon or bone marrow-derived macrophages (BMDMs) cocultured with CD200(+) cells. We found that Cd200(-/-) mice displayed diminished severity of colitis when compared to WT mice. Inflammation significantly diminished CD200 expression in WT mice, particularly on vascular endothelial cells and immune cells. The co-culture of BMDMs with CD200(+) cells inhibited TNF-alpha secretion. In vivo, acute colitis induced by DSS significantly increased TNF-alpha secretion in colon tissue in comparison to untreated controls. However, Cd200(-/-) mice secreted a similar level of TNF-alpha to WT mice in vivo. CD200 regulates the severity of DSS-induced colitis in conventionally-reared mice. The presence of CD200(+) cells decreases TNF-alpha production by macrophages in vitro. However, during DDS-induced intestinal inflammation secretion of TNF-alpha is independent of CD200 expression.