Role of type 2 immunity in intestinal inflammation

Type 2 (Th2) immune responses play important roles in intestinal immunity by contributing to the maintenance of mucosal homeostasis, not only conferring protection against helminthic infection but also participating in pro-inflammatory pathways in chronic intestinal inflammatory disorders, including inflammatory bowel disease. The current review focuses on recent developments regarding the role of Th2 responses in intestinal inflammation.

Th2 gut mucosal responses are promoted by mediators that are released following injury to the epithelium, and act as alarmin-type danger signals. Interleukin (IL)-33 is prominent among such factors and demonstrates a dichotomous function, exerting either protective or pro-inflammatory effects, depending on its cellular compartmentalization. The pool of type 2 effector cells has been enriched recently to include not only classical CD4+ Th2 lymphocytes but also a subset of innate lymphocytes (ILC2s) that express the transcriptional factor GATA binding protein 3 and secrete IL-4, IL-5, and IL-13. ILC2s play important roles during infection with helminths and bi-directionally interact with Th2 CD4+ lymphocytes, thus establishing a transition from innate to adaptive immunological pathways. Th2 responses are also involved in pro-inflammatory pathways at the intestinal mucosa, and neutralization of the pivotal cytokines IL-4 and IL-13 has been shown to regulate experimental intestinal inflammation. In striking contrast, however, neutralization of human IL-13 had no therapeutic effect in patients with ulcerative colitis.

Further studies will be required to delineate the specific mechanisms of type 2 mucosal immunity in inflammatory bowel disease and examine the applicability of Th2-targeted therapies for intestinal inflammation.