title: MyD88 in donor bone marrow cells is critical for protection from acute intestinal graft-vs.-host disease.
abstract: To understand the role of myeloid differentiation factor 88 (MyD88) expressed by donor bone marrow (BM) in the pathophysiology of graft-vs.-host disease (GVHD), we investigated the effects of transplantation of MyD88-deficient T cell-depleted BM (MyD88KO TCD-BM) on the severity of GVHD. Transplantation with MyD88KO TCD-BM aggravated GVHD; serious gut damage was evident, with high infiltration of T cells into the intestines of recipients and markedly reduced expansion of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). MDSCs from MyD88KO mice were defective in inducing donor T-cell apoptosis and inhibiting T-cell proliferation. Supplementation of transplanted mice with MDSCs from wild-type mice, but not MyD88KO mice, attenuated GVHD severity with reduced intestinal T-cell infiltration in MyD88KO TCD-BM recipients. Pretreatment of BM donors with lipopolysaccharide to increase MDSC levels and MyD88 transcription in the TCD-BM transplant alleviated GVHD severity and intestinal T-cell infiltration. The T cell/MDSC ratios were correlated with intestinal GVHD severity in both animal models and human patients. This study indicates that MyD88-dependent MDSC expansion from donor BM is critical for protection against fatal intestinal GVHD.
authors.affiliation: Departments of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Y-K
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Departments of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: S-E
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: J-M
authors.initials: JM
authors.lastname: Ju
authors.affiliation: Departments of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: K-S
authors.initials: KS
authors.lastname: Eom
authors.affiliation: Departments of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Departments of Pediatrics, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: N-G
authors.initials: NG
authors.lastname: Chung
authors.affiliation: Departments of Pediatrics, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: D C
authors.initials: DC
authors.lastname: Jeong
authors.affiliation: Departments of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: G
authors.initials: G
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: E Y
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Departments of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: C-K
authors.initials: CK
authors.lastname: Min
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D011183:Postoperative Complications / Q000276:immunology* / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D053594:Myeloid Differentiation Factor 88