TY - JOUR
T1 - Reciprocal expression of enteric antimicrobial proteins in intestinal graft-versus-host disease
AU - Eriguchi, Yoshihiro
AU - Uryu, Hidetaka
AU - Nakamura, Kiminori
AU - Shimoji, Sonoko
AU - Takashima, Shuichiro
AU - Iwasaki, Hiromi
AU - Miyamoto, Toshihiro
AU - Shimono, Nobuyuki
AU - Hashimoto, Daigo
AU - Akashi, Koichi
AU - Ayabe, Tokiyoshi
AU - Teshima, Takanori
N1 - Funding Information:
The authors thank Kiyoshi Takeda (Osaka University, Osaka, Japan) for providing MyD88 −/− mice. This study was supported by grants from JSPS KAKENHI ( 25293217 to T.T., 23390193 to T.A., and 22592029 to K.N.), Health and Labor Science Research Grants (T.T.), the Foundation for Promotion of Cancer Research (Tokyo, Japan) (to T.T.), the Northern Advancement Center for Science & Technology (Sapporo, Japan) (to T.A.), Yakult Bio-Science Foundation (Tokyo, Japan) (to T.T.), and SENSHIN Medical Research Foundation (to T.T.).
PY - 2013/10
Y1 - 2013/10
N2 - We recently demonstrated that expression of α-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 IIIγ (RegIIIγ) was upregulated in villous enterocytes, thus demonstrating the reciprocal control of enteric antimicrobial proteins in GVHD. Upregulation of RegIIIγ was mediated by a mechanism independent upon radiation-induced intestinal tract damage. MyD88-mediated signaling in intestinal epithelium was required for RegIIIγ upregulation in GVHD and antibiotic therapy downregulated RegIIIγ expression. These results suggest that MyD88-mediated sensing of the intestinal microbes disregulated in GVHD induces RegIIIγ upregulation in GVHD and argue a role for RegIIIγ in the pathogenesis of GVHD.
AB - We recently demonstrated that expression of α-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 IIIγ (RegIIIγ) was upregulated in villous enterocytes, thus demonstrating the reciprocal control of enteric antimicrobial proteins in GVHD. Upregulation of RegIIIγ was mediated by a mechanism independent upon radiation-induced intestinal tract damage. MyD88-mediated signaling in intestinal epithelium was required for RegIIIγ upregulation in GVHD and antibiotic therapy downregulated RegIIIγ expression. These results suggest that MyD88-mediated sensing of the intestinal microbes disregulated in GVHD induces RegIIIγ upregulation in GVHD and argue a role for RegIIIγ in the pathogenesis of GVHD.
KW - Defensins
KW - Graft-versus-host disease
KW - Hematopoietic stem cell transplantation
KW - Regenerating islet-derived III
KW - Toll-like receptors
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U2 - 10.1016/j.bbmt.2013.07.027
DO - 10.1016/j.bbmt.2013.07.027
M3 - Article
C2 - 23927965
AN - SCOPUS:84884180619
SN - 1083-8791
VL - 19
SP - 1525
EP - 1529
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 10
ER -