Mucosal neutrophils in acute colitis offer a protective role

▸ Zindl CL, Lai JF, Lee YK, et al. IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis. Proc Natl Acad Sci USA 2013;110:12768–73.

Interleukin 22 (IL-22) belongs to the IL-10 cytokine family and is known to play an important role in mucosal epithelial cell homeostasis. It has pro-inflammatory as well as tissue protective roles, promoting mucosal epithelial antimicrobial defence and mucosal barrier integrity. Studies have shown that in acute models of colitis, MyD88/TNF-α signals, triggered by microbial insults, result both in recruitment of macrophages and granulocytes and also increased IL-22 production. Recently, it has been demonstrated that neutrophils also play a protective role in the host response in acute models of colitis and play a dual role in host protection: opsonisation (direct killing of microbes) and also indirectly signalling via IL-22 to amplify antimicrobial peptide production and enhance barrier function. This recent study by Zindl and colleagues used a DSS-induced colitis model to demonstrate that colon-infiltrating neutrophils produce IL-22 in response to co-ordinated signalling by IL-23 and TNF-α. The study demonstrates that colon-recruited neutrophils are a critical source of IL-22 for restoration of epithelial integrity and suggests that sustained IL-22 production requires interplay with other IL-22 producing immune cells including NK cells, dendritic cells and γδ T cells. Although neutrophils are short-lived non-resident cells within the colon, the study highlights a previously unidentified connection in the Th17-neutrophil axis, as neutrophils also express IL-17 in response to IL-23. It is therefore possible that sustained recruitment of neutrophils resulting from Th17-driven chronic inflammation could be an important player in defining protective effects on the epithelium in situations of colonic injury such as inflammatory bowel disease (IBD).

The role of caspase recruitment domain/caspase-1/IL-1β complex signalling in hepatic ischaemia/reperfusion injury

▸ Kamo N, Ke B, Ghaffari AA, et al. ASC/caspase-1/IL-1β signalling triggers inflammatory responses by promoting HMGB1 induction in liver …