Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for multiple sclerosis.
Human mesenchymal stem cells (hMSCs) are being considered for clinical trials of multiple sclerosis (MS). We examined the effects of adult bone marrow-derived hMSCs on responses of primary human Th1, Th17, and Th1/17 double-expressing T-cell subsets, all implicated in MS. As expected, soluble products from hMSCs inhibited Th1 responses; however, Th17 responses were increased. Secretion of interleukin (IL)-10, considered anti-inflammatory, was decreased. Pretreating hMSCs with the proinflammatory cytokine IL-1β accentuated these effects, and caused decreases in the Th1/17 subset. These findings underscore the importance of further preclinical work and immune-monitoring to define hMSC effects on disease-relevant immune responses under variable conditions.
Darlington
Peter J
PJ
Neuroimmunology Unit, Montreal Neurological Institute, Montreal, Quebec, Canada.
Boivin
Marie-Noëlle
MN
Renoux
Christel
C
François
Moïra
M
Galipeau
Jacques
J
Freedman
Mark S
MS
Atkins
Harold L
HL
Cohen
Jeffrey A
JA
Solchaga
Luis
L
Bar-Or
Amit
A
D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D016207:Cytokines