title: Mesenchymal stem cells derived from human induced pluripotent stem cells modulate T-cell phenotypes in allergic rhinitis.
abstract: BACKGROUND
  Human induced pluripotent stem cells (iPSCs) possess remarkable self-renewal capacity and the potential to differentiate into novel cell types, such as mesenchymal stem cells (MSCs). iPSC-MSCs have been shown to enhance tissue regeneration and attenuate tissue ischaemia; however, their contribution to the immune regulation of Th2-skewed allergic rhinitis (AR) and asthma remains unclear.
  
  
  OBJECTIVE
  This study compared the immunomodulatory effects of iPSC-MSCs and bone marrow-derived MSCs (BM-MSCs) on lymphocyte proliferation, T-cell phenotypes and cytokine production in peripheral blood mononuclear cells (PBMCs) in patients with AR, and investigated the possible molecular mechanisms underlying the immunomodulatory properties of iPSC-MSCs.
  
  
  METHODS
  In co-cultures of PBMCs with iPSC-MSCs or BM-MSCs, lymphocyte proliferation was evaluated using 3H-thymidine (3H-TdR) uptake, carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE) assays; the regulatory T-cell (Treg) phenotype was determined by flow cytometry, and cytokine levels were measured using an enzyme-linked immunosorbent assay. The immunomodulatory properties of both MSCs were further evaluated using NS398 and transwell experiments.
  
  
  RESULTS
  Similar to BM-MSCs, we determined that iPSC-MSCs significantly inhibit lymphocyte proliferation and promote Treg response in PBMCs (P < 0.05). Accordingly, the cytokine milieu (IFN-γ, IL-4, IL-5, IL-10 and IL-13) in the supernatants of PBMCs changed significantly (P < 0.05). The immunomodulatory properties of iPSC-MSCs and BM-MSCs were associated with prostaglandin E2 (PGE2) production and cell-cell contact.
  
  
  CONCLUSIONS
  These data demonstrate that iPSC-MSCs are capable of modulating T-cell phenotypes towards Th2 suppression through inducing Treg expansion, suggesting that iPSC-MSCs can be used as an alternative candidate to adult MSCs to treat allergic airway diseases.
authors.affiliation: Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong.
authors.forename: Q L
authors.initials: QL
authors.lastname: Fu
authors.forename: Y Y
authors.initials: YY
authors.lastname: Chow
authors.forename: S J
authors.initials: SJ
authors.lastname: Sun
authors.forename: Q X
authors.initials: QX
authors.lastname: Zeng
authors.forename: H B
authors.initials: HB
authors.lastname: Li
authors.forename: J B
authors.initials: JB
authors.lastname: Shi
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Sun
authors.forename: W
authors.initials: W
authors.lastname: Wen
authors.forename: H F
authors.initials: HF
authors.lastname: Tse
authors.forename: Q
authors.initials: Q
authors.lastname: Lian
authors.forename: G
authors.initials: G
authors.lastname: Xu
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D056747:Immunomodulation; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000209:etiology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology