title: CCR7 expressing mesenchymal stem cells potently inhibit graft-versus-host disease by spoiling the fourth supplemental Billingham's tenet.
abstract: The clinical acute graft-versus-host disease (GvHD)-therapy of mesenchymal stem cells (MSCs) is not as satisfactory as expected. Secondary lymphoid organs (SLOs) are the major niches serve to initiate immune responses or induce tolerance. Our previous study showed that CCR7 guide murine MSC line C3H10T1/2 migrating to SLOs. In this study, CCR7 gene was engineered into murine MSCs by lentivirus transfection system (MSCs/CCR7). The immunomodulatory mechanism of MSCs/CCR7 was further investigated. Provoked by inflammatory cytokines, MSCs/CCR7 increased the secretion of nitric oxide and calmed down the T cell immune response in vitro. Immunofluorescent staining results showed that transfused MSCs/CCR7 can migrate to and relocate at the appropriate T cell-rich zones within SLOs in vivo. MSCs/CCR7 displayed enhanced effect in prolonging the survival and alleviating the clinical scores of the GvHD mice than normal MSCs. Owing to the critical relocation sites, MSCs/CCR7 co-infusion potently made the T cells in SLOs more naïve like, thus control T cells trafficking from SLOs to the target organs. Through spoiling the fourth supplemental Billingham's tenet, MSCs/CCR7 potently inhibited the development of GvHD. The study here provides a novel therapeutic strategy of MSCs/CCR7 infusion at a low dosage to give potent immunomodulatory effect for clinical immune disease therapy.
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100850, People's Republic of China; Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, Beijing 100071, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The Second Artillery General Hospital, Beijing 100088, People's Republic of China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Sun
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Rui-Jie
authors.initials: RJ
authors.lastname: Dang
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, Beijing 100071, People's Republic of China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Ning
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, Beijing 100071, People's Republic of China.
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100850, People's Republic of China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Jiang
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100850, People's Republic of China.
authors.forename: Xi-Min
authors.initials: XM
authors.lastname: Guo
authors.affiliation: Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wen
authors.affiliation: Department of Plastic and Reconstructive Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100850, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Mao
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Affiliated Hospital to Academy of Military Medical Sciences, Beijing 100071, People's Republic of China.
authors.forename: Hu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100850, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002465:Cell Movement; D006086:Graft vs Host Disease / Q000517:prevention & control*; D056747:Immunomodulation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse