Details

Autor(en) / Beteiligte

• Zhao, Dongchang
• Kim, Yeung-Hyen
• Jeong, Seihwan
• Greenson, Joel K
• Chaudhry, Mohammed S
• Hoepting, Matthias
• Anderson, Erik R
• van den Brink, Marcel Rm
• Peled, Jonathan U
• Gomes, Antonio Lc
• Slingerland, Ann E
• Donovan, Michael J
• Harris, Andrew C
• Levine, John E
• Ozbek, Umut
• Hooper, Lora V
• Stappenbeck, Thaddeus S
• Ver Heul, Aaron
• Liu, Ta-Chiang
• Reddy, Pavan
• Ferrara, James Lm

Titel

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

Ist Teil von

• The Journal of clinical investigation, 2018-11, Vol.128 (11), p.4970-4979

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.