作者
Andrea S Henden, Motoko Koyama, Renee J Robb, Adriana Forero, Rachel D Kuns, Karshing Chang, Kathleen S Ensbey, Antiopi Varelias, Stephen H Kazakoff, Nicole Waddell, Andrew D Clouston, Rabina Giri, Jakob Begun, Bruce R Blazar, Mariapia A Degli-Esposti, Sergei V Kotenko, Steven W Lane, Kate L Bowerman, Ram Savan, Philip Hugenholtz, Kate H Gartlan, Geoffrey R Hill
发表日期
2021/8/26
期刊
Blood, The Journal of the American Society of Hematology
卷号
138
期号
8
页码范围
722-737
出版商
American Society of Hematology
简介
Immunopathology and intestinal stem cell (ISC) loss in the gastrointestinal (GI) tract is the prima facie manifestation of graft-versus-host disease (GVHD) and is responsible for significant mortality after allogeneic bone marrow transplantation (BMT). Approaches to prevent GVHD to date focus on immune suppression. Here, we identify interferon-λ (IFN-λ; interleukin-28 [IL-28]/IL-29) as a key protector of GI GVHD immunopathology, notably within the ISC compartment. Ifnlr1−/− mice displayed exaggerated GI GVHD and mortality independent of Paneth cells and alterations to the microbiome. Ifnlr1−/− intestinal organoid growth was significantly impaired, and targeted Ifnlr1 deficiency exhibited effects intrinsic to recipient Lgr5+ ISCs and natural killer cells. PEGylated recombinant IL-29 (PEG-rIL-29) treatment of naive mice enhanced Lgr5+ ISC numbers and organoid growth independent of both IL-22 and type I IFN …
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AS Henden, M Koyama, RJ Robb, A Forero, RD Kuns… - Blood, The Journal of the American Society of …, 2021