地穴
细胞凋亡
生物
移植物抗宿主病
胃肠道
免疫学
干细胞
移植
潘尼斯电池
癌症研究
细胞生物学
医学
内科学
小肠
内分泌学
遗传学
生物化学
作者
Di Zhao,Yeung‐Hyen Kim,Seihwan Jeong,Joel K. Greenson,Mohammed S. Chaudhry,Matthias Hoepting,Erik R. Anderson,Marcel R.M. van den Brink,Jonathan U. Peled,António Gomes,Ann E. Slingerland,Michael Donovan,Andrew C. Harris,John E. Levine,Umut Özbek,Lora V. Hooper,Thaddeus S. Stappenbeck,Aaron M. Ver Heul,Ta‐Chiang Liu,Pavan Reddy,James L.M. Ferrara
摘要
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.
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