Mucosal IgG in inflammatory bowel disease – a question of (sub)class?

Abstract

Immunoglobulins (Igs) form a cornerstone of mucosal immunity. In the gastrointestinal tract, secretory IgA and IgM bind to commensal microorganisms within the intestinal lumen to prevent them from breaching the intestinal epithelium – a process known as immune exclusion. In recent years, there has been renewed interest in the role of IgG in intestinal immunity, driven in part by a genetic association of an affinity-lowering variant of an IgG receptor, FcγRIIA, with protection from ulcerative colitis (UC), a subclass of inflammatory bowel disease (IBD). We recently demonstrated a role for IgG and Fcγ receptor signalling in driving pathogenic IL-1β production by colonic mononuclear phagocytes and the subsequent induction of a local type 17 response in UC. Here, we discuss the potential relevance of our observations to the other major subclass of IBD – Crohn’s disease (CD) – where the genetic association with FCGR variants is less robust and consider how this may impact therapeutic interventions in these disease subsets.

Keywords

• igg
• fcγ receptors
• inflammatory bowel disease
• ulcerative colitis
• crohn’s disease
• subclasses