The number of regulatory T (Treg) cells in the spleens of mice with colitis and levels of IL-4 both increased following treatment with M2b macrophage exosomes.
In vivo IL-4 administration initiated 10 days after infection increased mucus thickness and quality and decreased colitis and pathogen contact with the epithelium.
We have previously observed that STAT6-/- mice present delayed mucosal recovery after 2,4,6-trinitrobenzenesulfonic acid [TNBS]-induced colitis due to a deficiency in reparatory interleukin-4 [IL4]/STAT6-dependent M2 macrophages, which can be reverted by the exogenous transfer of this cell type.
In contrast, transfer of CD4(+)CD62L(-) T cells from c-Maf transgenic, but not wild-type mice induced colitis and augmented colitis induced by CD4(+)CD62L(+) T cells from wild-type mice in an IL-4-independent pathway, as determined by macroscopic, histologic, and endoscopic criteria.
Furthermore, T-bet-deficient CD62L(-) CD4(+) T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-beta signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-gamma/IL-4 and TGF-beta responses and the development of chronic intestinal inflammation in T cell-mediated colitis.
Interleukin-4 (IL-4) is an important cytokine in mucosal immunity and plays a critical role in the development of colitis in T-alpha cell receptor mutant mice.