Regenerating Islet-Derived 3-Alpha (REG3A) Protects the Intestinal Stem Cell Niche to Control Acute Gastrointestinal Graft-Versus-Host Disease

Regenerating islet-derived 3 (Reg3γ), a Paneth cell antimicrobial peptide, is an important biomarker of GI GVHD (Ferrara, Blood, 2012) but its mechanistic role in GVHD is not known. Paneth cells decrease during severe GVHD in both clinical and experimental BMT, and therefore we evaluated whether the loss of Reg3γ would amplify GVHD severity. IL-22, the principle inducer of Reg3γ, decreased prior to loss of Reg3γ during GVHD (data not shown) and injections of IL-22 reversed ongoing GVHD in two GVHD models (Figure 1A,B).