Immunomodulatory properties of colonic mesenchymal stem cells.
OBJECTIVE
To elucidate the immunomodulatory functions of colonic mesenchymal stem cells (MSCs) in the colonic mucosal immune system.


METHODS
The colonic MSCs were isolated, enriched and expanded. The immunosuppressive role of colonic MSCs on activated T cells was evaluated. The cell cycle progression of T cells and the expression of FoxP3+ T cells were assessed by fluorescence-activated cell sorting (FACS). The levels of cytokines and PGE2 were measured by ELISA.


RESULTS
Mouse colonic MSCs can inhibit the proliferation of activated T cells by arresting cells in G0/G1 phase, induce the expression of CD4+CD25+Foxp3+ T cells (8.05%±0.49% in transwell culture vs 8.45%±0.64% in direct contact culture vs 4.30%±0.28% in control, p<0.05), downregulate the levels of the cytokines TNF-α and IFN-γ, and increase the production of IL-10 (p<0.05). The data obtained from transwell culture and direct contact culture showed no difference (p>0.05). PGE2 level was increased when T cells were cultured with colonic MSCs (385.10±19.45 ng/l in transwell culture vs 387.91±19.85 ng/l in direct contact culture vs 276.21±25.49 ng/l in control, p<0.05). Blocking PGE2 partially reversed the immunosuppression of MSCs on activated T cells proliferation (p<0.05).


CONCLUSIONS
Colonic MSCs have the same immunosuppressive property as other MSCs. They performed their functions partially through secreting soluble factor PGE2. The characterization of these colonic MSCs may be helpful for studying the involvement of stromal cell compartment in colon diseases.
Department of Gastroenterology, West China Hospital of Sichuan University, 37 Guoxue Street, Chengdu 610041, China.
Jia
J
Hu
Xin
X
Zhang
Liping
L
Zhou
Yan
Y
Zhang
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D059447:Cell Cycle Checkpoints / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003106:Colon / Q000166:cytology / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D016193:G1 Phase / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D015232:Dinoprostone
Colon; Immunoloregulation; Mesenchymal stem cell