Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 19, Issue 10, Pages 1525-1529Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2013.07.027
Keywords
Hematopoietic stem cell transplantation; Graft-versus-host disease; Regenerating islet-derived III; Defensins; Toll-like receptors
Categories
Funding
- JSPS KAKENHI [25293217, 23390193, 22592029]
- Health and Labor Science Research Grants
- Foundation for Promotion of Cancer Research (Tokyo, Japan)
- Northern Advancement Center for Science & Technology (Sapporo, Japan)
- Yakult Bin-Science Foundation (Tokyo, Japan)
- SENSHIN Medical Research Foundation
- Grants-in-Aid for Scientific Research [25293217, 24790977, 24659463, 22592029, 25670443, 23390193] Funding Source: KAKEN
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We recently demonstrated that expression of alpha-defensins, the major antimicrobial peptides produced by Paneth cells, was severely suppressed in mice with graft-versus-host disease (GVHD). In this study, we found that antibacterial lectin, regenerating islet-derived III gamma (RegIII gamma) was upregulated in villous enterocytes, thus demonstrating the reciprocal control of enteric antimicrobial proteins in GVHD. Upregulation of RegIII gamma was mediated by a mechanism independent upon radiation-induced intestinal tract damage. MyD88-mediated signaling in intestinal epithelium was required for RegIII gamma upregulation in GVHD and antibiotic therapy downregulated RegIII gamma expression. These results suggest that MyD88-mediated sensing of the intestinal microbes disregulated in GVHD induces RegIII gamma upregulation in GVHD and argue a role for RegIII gamma in the pathogenesis of GVHD. (C) 2013 American Society for Blood and Marrow Transplantation.
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