Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. IL-10 receptor (IL-10R) consists of two chains of ligand-binding IL-10RA and two subunits of IL-10RB. IL-10 and IL-10R play important role in maintaining immune homeostasis in the gastrointestinal tract. Mutations in the IL10, IL10R cause spontaneous colitis in mice model and very early onset inflammatory bowel disease (VEOIBD) in human. Patients who have disease onset before 6 years of age are defined as VEOIBD. IL10 and IL10 receptor defect are classified as one type of monogenic inborn errors of immunity (IEI). IL-10 signalling defects demonstrate a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Patients develop symptoms during infancy and have more severe phenotype than polygenic inflammatory bowel disease (IBD). Here, we review the recent advances in the genetic mechanism, population dynamics and innate and adaptive immune dysregulation and interactions of gut microbiota regarding IL-10 signalling defects. The understanding of the pathogenesis has informed therapeutic strategies including haematopoietic stem cell transplant and novel biologics such as interleukin 1 receptor antagonist. Optimised transplant regimen and decreased risk of graft versus host disease with gut immunomodulation with vedolizumab might be used to improve transplant outcomes. More recently, gene therapy and gene editing have become treatment options for a range of IEIs, however evidence for IL-10 signalling defects is limited to in vitro and in vivo models. Beyond the Mendelian disorders, IL-10 signalling and neutralizing autoantibodies against IL-10 is relevant to the pathogenesis of polygenic IBD.
Xiao et al. (Thu,) studied this question.