Mesenchymal stem cells alter migratory property of T and dendritic cells to delay the development of murine lethal acute graft-versus-host disease.
Due to the potent immunoregulatory capacity, mesenchymal stem cells (MSCs) have been used in clinical trials to treat acute graft-versus-host disease (aGvHD), although the detailed in vivo mechanisms remain elusive. In a murine lethal aGvHD model, MSCs delayed the development of the disease. Interestingly, we found that MSC infusion increased the number of T lymphocytes in the secondary lymphoid organs (SLOs). Since the expression of CD62L and CCR7 is prerequisite for lymphocyte migration into SLOs, the in vitro experiments revealed that in the presence of MSCs, T lymphocytes (including CD4(+)CD25(+) regulatory T cells) preferred to take the naive-like phenotype (CD62L(+)/CCR7(+)) in mixed lymphocyte reaction and maintained the migratory activity elicited by secondary lymphoid tissue chemokine (SLC). Dendritic cells (DCs) are the initiator of immune response. CCR7 expression is pivotal for their maturation and migration into SLOs. However, CCR7 expression and SLC-driven migratory activity of DCs were remarkably suppressed by MSC coculture. The processes above were realized mainly through secretory mechanism. Consistently, MSC infusion maintained T lymphocytes to take CD62L(+)/CCR7(+) phenotype and decreased the CCR7 expression and proportion of DCs in SLOs of aGvHD mice. In conclusion, the altered migratory properties of T cells and DCs might contribute to the immunosuppressive activity of transplanted MSCs in the setting of aGvHD. Disclosure of potential conflicts of interest is found at the end of this article.
Li
Hong
H
Department of Cell Biology, Institute of Basic Medical Sciences, Beijing, China. maoning@nic.bmi.ac.cn
Guo
ZiKuan
Z
Jiang
XiaoXia
X
Zhu
Heng
H
Li
XiuSen
X
Mao
Ning
N
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002465:Cell Movement; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology*; D007262:Infusions, Intravenous; D019041:L-Selectin / Q000378:metabolism; D018655:Lymphocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D054400:Receptors, CCR7 / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D013347:Subcellular Fractions / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D015703:Antigens, CD; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019041:L-Selectin; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein