| First Author | Zhao D | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 11 | Pages | 4970-4979 |
| PubMed ID | 30106382 | Mgi Jnum | J:271106 |
| Mgi Id | MGI:6279662 | Doi | 10.1172/JCI99261 |
| Citation | Zhao D, et al. (2018) Survival signal REG3alpha prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease. J Clin Invest 128(11):4970-4979 |
| abstractText | Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract remains the major cause of morbidity and nonrelapse mortality after BM transplantation (BMT). The Paneth cell protein regenerating islet-derived 3alpha (REG3alpha) is a biomarker specific for GI GVHD. REG3alpha serum levels rose in the systematic circulation as GVHD progressively destroyed Paneth cells and reduced GI epithelial barrier function. Paradoxically, GVHD suppressed intestinal REG3gamma (the mouse homolog of human REG3alpha), and the absence of REG3gamma in BMT recipients intensified GVHD but did not change the composition of the microbiome. IL-22 administration restored REG3gamma production and prevented apoptosis of both intestinal stem cells (ISCs) and Paneth cells, but this protection was completely abrogated in Reg3g-/- mice. In vitro, addition of REG3alpha reduced the apoptosis of colonic cell lines. Strategies that increase intestinal REG3alpha/gamma to promote crypt regeneration may offer a novel, nonimmunosuppressive approach for GVHD and perhaps for other diseases involving the ISC niche, such as inflammatory bowel disease. |
