Fetal BM-derived mesenchymal stem cells promote the expansion of human Th17 cells, but inhibit the production of Th1 cells.
Th type 17 (Th17) cells have been identified as a proinflammatory T-cell subset. Here, we investigated the regulation of human Th17 cells by fetal BM-derived mesenchymal stem cells (FBM-MSC). We cocultured FBM-MSC with human PBMC or CD4(+) T cells from healthy donors. FBM-MSC significantly suppressed the proliferation of CD4(+) T cells stimulated by PHA and recombinant IL-2. Significantly higher levels of IL-17 were observed in FBM-MSC cocultured with either PBMC or CD4(+) T cells than that in PBMC cultured alone or CD4(+) T cells cultured alone. Flow cytometry analysis showed that the percentage of Th17 cells in coculture of FBM-MSC and CD4(+) T cells was significantly higher than that in CD4(+) T-cell cultured alone. FBM-MSC did not express IL-17 protein. Consistent with the augmentation of Th17 cells, significantly higher levels of IL-6 and IL-1 were observed in coculture of FBM-MSC and CD4(+) T cells than that in CD4(+) T-cell culture, while the levels of IL-23 were similar between FBM-MSC + PBMC coculture and PBMC alone, or FBM-MSC + CD4(+) T-cell and CD4(+) T-cell alone. The presence of FBM-MSC decreased the percentage of Th1 cells, but minimally affected the expansion of CD4(+)CD25(+) T cells. In conclusion, our data demonstrate for the first time that FBM-MSC promote the expansion of Th17 cells and decrease IFN-gamma-producing Th1 cells. These data suggest that IL-6 and IL-1, instead of IL-23, may be partly involved in the expansion of Th17 cells.
Guo
Zhenxing
Z
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, P R China.
Zheng
Cuiling
C
Chen
Zhenping
Z
Gu
Dongsheng
D
Du
Weiting
W
Ge
Jing
J
Han
Zhongchao
Z
Yang
Renchi
R
D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D053686:Fetal Stem Cells / Q000737:chemistry / Q000166:cytology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000494:pharmacology; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology
D015703:Antigens, CD; C508600:IL6 protein, human; D007375:Interleukin-1; D020381:Interleukin-17; D007376:Interleukin-2; D053759:Interleukin-23; D015850:Interleukin-6; D010835:Phytohemagglutinins; D007371:Interferon-gamma