Sa1773 Caspase-11 Enhances Killing of Colitogenic Escherichia Coli by Macrophages, but Does Not Affect Development of Experimental Colitis

WT Balb/C mice (p<0.001 for each cytokine btw uninfected control and helminth-infected; N=at least 3 independent experiments), while no regulation of IFNγ and modest induction of IL4 or IL10 was seen in STAT6-/mice. Helminths did not induce TGFβ production in STAT6-/animals. In an acute GVHD and colitis model, helminths regulated WT donor T cell Th1 cytokine generation, serum Th1 cytokines, colitis and survival in WT and not STAT6-/recipients (p<0.05 for each parameter btw. helminth infected WT and helminthinfected STAT6-/recipients, multiple experiments). Helminth infection was associated with the induction of donor and recipient FoxP3+ regulatory T cells (Tregs) in WT and not STAT6-/bone marrow transplanted mice (p<0.05 btw. helminth infected WT and helminthinfected STAT6-/recipients, multiple experiments). Addition of TGFβ to STAT6-/T cell cultures restored T cell IL10 production and Treg generation that regulate Th1 inflammation. Conclusions: STAT6 is a critical transcription factor directing mucosal TGFβ producing Th3 cell generation. Helminths utilize STAT6 pathway to induce mucosal Tregs, trigger mucosal T cell IL10 secretion and regulate alloreactive colitis in a TGFβ dependent manner.