They’re bugs, Jim, but not as we know them ▸

A theme is evolving in the pathogenesis of chronic inflammation seen in colitis and Crohn’s disease and it points to bacterial flagellin. The dependence of inflammatory bowel disease (IBD) on intestinal microbes is increasingly clear but the molecular mechanisms are not. CD4⁺ T cell lymphocytes directed against enteric microbiota are crucial effector cells in experimental models of IBD. Enteric bacterial antigen reactive CD4⁺ T cells are able to induce colitis when transferred to immunodeficient recipients. There is a relatively small number of immunodominant antigens that stimulate pathological T cell responses and attention was drawn in a previous issue of JournalScan to a paper in PNAS that identified an epitope on the flagellar hook protein of Helicobacter hepaticus as a precipitant of colitis. The current paper from Birmingham Alabama and Los Angeles initially identified specific bacterial antigens driving experimental IBD by a technique called serological position cloning which screens DNA libraries with defined antisera. Strong reactivity against specific flagellins was seen in many models of colitis. They then demonstrated that flagellin specific …