title: Mesenchymal stromal cells inhibit Th17 but not regulatory T-cell differentiation.
abstract: OBJECTIVE
  A previous study has demonstrated that mouse mesenchymal stromal cells (MSC) produce nitric oxide (NO), which suppresses signal transducer and activator of transcription (STAT) 5 phosphorylation and T-cell proliferation under neutral and T helper 1 cells (Th1) conditions. We aimed to determine the effects of MSC on T helper 17 cells (Th17) and regulatory T-cell (T-reg) differentiation.
  
  
  METHODS
  CD4 T cells obtained from mouse spleen were cultured in conditions for Th17 or Treg differentiation with or without mouse MSC. Th17 and Treg differentiation was assessed by flow cytometry using antibodies against interleukin (IL)-17 and forkhead box P3 (Foxp3), a master regulator of Treg cells.
  
  
  RESULTS
  MSC inhibited Th17 but not Treg differentiation. Under Th17 conditions, MSC did not produce NO, and inhibitors of indoleamine-2,3-dioxygenase (IDO) and prostaglandin E(2) (PGE2) both restored MSC suppression of differentiation, suggesting that MSC suppress Th17 differentiation at least in part through PGE2 and IDO.
  
  
  CONCLUSIONS
  Our results suggest that MSC regulate CD4 differentiation through different mechanisms depending on the culture conditions.
authors.affiliation: Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Raine
authors.initials: R
authors.lastname: Tatara
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Keiko
authors.initials: K
authors.lastname: Hatanaka
authors.forename: Iekuni
authors.initials: I
authors.lastname: Oh
authors.forename: Akiko
authors.initials: A
authors.lastname: Meguro
authors.forename: Haruko
authors.initials: H
authors.lastname: Matsu
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sato
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D015232:Dinoprostone; D000098546:Interleukin-21