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

Overview

MeSH Major

  • Clostridium Infections
  • Clostridium difficile
  • Hematopoietic Stem Cell Transplantation

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.

publication date

  • November 2018

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC6205404

Digital Object Identifier (DOI)

  • 10.1172/JCI99261

PubMed ID

  • 30106382

Additional Document Info

start page

  • 4970

end page

  • 4979

volume

  • 128

number

  • 11