Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease Journal Article


Authors: Zhao, D.; Kim, Y. H.; Jeong, S.; Greenson, J. K.; Chaudhry, M. S.; Hoepting, M.; Anderson, E. R.; van den Brink, M. R.; Peled, J. U.; Gomes, A. L.; Slingerland, A. E.; Donovan, M. J.; Harris, A. C.; Levine, J. E.; Ozbek, U.; Hooper, L. V.; Stappenbeck, T. S.; Ver Heul, A.; Liu, T. C.; Reddy, P.; Ferrara, J. L.
Article Title: Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease
Abstract: 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 3α (REG3α) is a biomarker specific for GI GVHD. REG3α serum levels rose in the systematic circulation as GVHD progressively destroyed Paneth cells and reduced GI epithelial barrier function. Paradoxically, GVHD suppressed intestinal REG3γ (the mouse homolog of human REG3α), and the absence of REG3γ in BMT recipients intensified GVHD but did not change the composition of the microbiome. IL-22 administration restored REG3γ 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 REG3α reduced the apoptosis of colonic cell lines. Strategies that increase intestinal REG3α/γ 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.
Keywords: transplantation; immunology; innate immunity; adaptive immunity; bone marrow transplantation
Journal Title: Journal of Clinical Investigation
Volume: 128
Issue: 11
ISSN: 0021-9738
Publisher: American Society for Clinical Investigation  
Date Published: 2018-11-01
Start Page: 4970
End Page: 4979
Language: English
DOI: 10.1172/jci99261
PUBMED: 30106382
PROVIDER: scopus
PMCID: PMC6205404
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Jonathan U Peled
    34 Peled
  2. Antonio LC Gomes
    7 Gomes