title: Alleviation of skin inflammation after Lin(-) cell transplantation correlates with their differentiation into myeloid-derived suppressor cells.
abstract: To understand the cellular mechanism underlying the therapeutic effects exerted by hematopoietic stem cell transplantation in the repair of tissue damage, we investigated the in vivo dynamics of bone marrow (BM) lineage-negative (Lin(-)) cells transplanted into mice with hyper sensitivity dermatitis. Longitudinal in vivo imaging and flow cytometry analyses revealed that Lin(-) cells home directly to inflamed skin within 6 h, where they undergo extensive expansion with the peak on day 14 post-transplantation, and preferential differentiation into CD11b(+)Ly6G(int)Ly6C(+) cells by day 7. Cells with phenotypic profiles of neutrophils, macrophages, and DCs appeared in inflamed skin on day 14. Progenies of transplanted Lin(-) cells showed similar kinetics of expansion and myeloid differentiation in BM. However, differentiation into CD11b(+)Ly6G(int)Ly6C(+) cells in the inflamed skin on day 7 was more skewed toward CD115(+) cells (≥60%) with immune suppressive function and higher expression levels of iNOS, arginase, and IL-10, compared with those in the BM. Transplantation of Lin(-) cells reduced the levels of Cd3 transcript and CD4(+)/CD8(+) cells in inflamed skin. These results demonstrate differentiation of transplanted Lin(-) cells into myeloid-derived suppressor cells in inflamed skin to be the basis of the alleviation of skin inflammation after Lin(-) cell transplantation.
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Su
authors.initials: S
authors.lastname: Jeong Ryu
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Ju
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Woojin
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Bum Kim
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kuen
authors.initials: K
authors.lastname: Hee Oh
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong
authors.initials: D
authors.lastname: Sup Lee
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hakmo
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Ju
authors.initials: J
authors.lastname: Eun Oh
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyong
authors.initials: K
authors.lastname: Soo Park
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Eun
authors.initials: E
authors.lastname: Young Choi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D003872:Dermatitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004137:Dinitrochlorobenzene / Q000633:toxicity; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007124:Immunoenzyme Techniques; D007509:Irritants / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004137:Dinitrochlorobenzene; D007509:Irritants; D012333:RNA, Messenger