Reciprocal expression of enteric antimicrobial proteins in intestinal graft-versus-host disease.
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.
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan.
Yoshihiro
Y
Eriguchi
Hidetaka
H
Uryu
Kiminori
K
Nakamura
Sonoko
S
Shimoji
Shuichiro
S
Takashima
Hiromi
H
Iwasaki
Toshihiro
T
Miyamoto
Nobuyuki
N
Shimono
Daigo
D
Hashimoto
Koichi
K
Akashi
Tokiyoshi
T
Ayabe
Takanori
T
Teshima
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
D023181:Antimicrobial Cationic Peptides
Defensins; Graft-versus-host disease; Hematopoietic stem cell transplantation; Regenerating islet-derived III; Toll-like receptors