A study by Tom Castro-Dopico, a Wellcome Trust 3I PhD student and now a postdoc in Menna Clatworthy’s lab (Medicine), provides new insights into the mechanisms mediating inflammation in ulcerative colitis (UC).
Inflammatory bowel disease is a chronic, relapsing condition with two subtypes, Crohn’s disease and UC. Genetic studies in UC implicate an IgG antibody receptor variant, but why this affects inflammation in an IgA-dominated organ has been unclear.
Tom and colleagues uncovered a profound induction of anti-commensal IgG in the colonic mucosa of UC patients and outline a pathway whereby Fcγ-receptor activation by IgG leads to IL-1β production, type 17 immunity, and the exacerbation of inflammation.
The work, published in Immunity, identifies the cellular mechanisms by which variation in IgG receptor genes confer susceptibility to UC and has therapeutic implications. IgG and FcγR expression are particularly high in colonic biopsies of patients who are resistant to TNF-blocking treatments, suggesting that the FcγR-mediated pathway identified could be targeted in this patient group.