Il17d-flox Mouse

Il17d is a member of the interleukin-17 (IL-17) family of cytokines. The IL-17 family consists of six members (IL-17A to IL-17F), and while the functions of some family members like IL-17A and IL-17F are relatively well-characterized, those of Il17d had remained largely elusive. However, recent research has started to shed light on its functions [1].

In Il17d-/-mice (a gene knockout model), these animals were more susceptible to acute colitis, bacterial infection, and experimentally induced colon cancer compared to wild-type mice. Il17d deficiency impaired IL-22 production by group 3 innate lymphoid cells (ILC3s) and reduced the expression of IL-22-dependent antimicrobial peptides in the colon, associated with changes in microbial composition and dysbiosis. Protein purification studies showed that Il17d binds to CD93, a glycoprotein expressed on mature ILC3s, and mice lacking Cd93 in ILC3s also exhibited impaired IL-22 production and aggravated colonic inflammation [3]. Additionally, in keratinocytes, Il17d can induce the inhibition of DDX5 expression through the CD93-p38 MAPK-AKT-SMAD2/3 signaling pathway. This leads to pre-messenger RNA splicing events that selectively amplify IL-36R-mediated inflammatory responses and cutaneous inflammation [2].

In conclusion, Il17d plays a role in maintaining intestinal homeostasis by regulating ILC3 function through the Il17d-CD93 axis. In the skin, it can modulate keratinocyte-related inflammation. The use of Il17d gene knockout mouse models has been crucial in revealing its functions in colonic and skin-related disease conditions, highlighting its potential as a target for therapies related to these diseases.