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Interleukin-17A-Induced Human Mesenchymal Stem Cells Are Superior Modulators of Immunological Function.
Sivanathan, Kisha Nandini; Rojas-Canales, Darling M; Hope, Christopher M; Krishnan, Ravi; Carroll, Robert P; Gronthos, Stan; Grey, Shane T; Coates, Patrick T.
Afiliación
  • Sivanathan KN; School of Medicine, Faculty of Health Sciences, Adelaide, South Australia, Australia.
  • Rojas-Canales DM; Centre for Stem Cell Research and Robinson Institute, School of Medical Sciences, Adelaide, South Australia, Australia.
  • Hope CM; Centre for Clinical and Experimental Transplantation, Adelaide, South Australia, Australia.
  • Krishnan R; School of Medicine, Faculty of Health Sciences, Adelaide, South Australia, Australia.
  • Carroll RP; Centre for Clinical and Experimental Transplantation, Adelaide, South Australia, Australia.
  • Gronthos S; School of Medicine, Faculty of Health Sciences, Adelaide, South Australia, Australia.
  • Grey ST; Centre for Clinical and Experimental Transplantation, Adelaide, South Australia, Australia.
  • Coates PT; School of Medicine, Faculty of Health Sciences, Adelaide, South Australia, Australia.
Stem Cells ; 33(9): 2850-63, 2015 Sep.
Article en En | MEDLINE | ID: mdl-26037953
Interferon-γ (IFN-γ)-preactivated mesenchymal stem cells (MSC-γ) are highly immunosuppressive but immunogenic in vivo due to their inherent expression of major histocompatibility (MHC) molecules. Here, we present an improved approach where we modified human bone marrow-derived MSC with interleukin-17A (MSC-17) to enhance T cell immunosuppression but not their immunogenicity. MSC-17, unlike MSC-γ, showed no induction or upregulation of MHC class I, MHC class II, and T cell costimulatory molecule CD40, but maintained normal MSC morphology and phenotypic marker expression. When cocultured with phytohemagglutinin (PHA)-activated human T cells, MSCs-17 were potent suppressors of T cell proliferation. Furthermore, MSC-17 inhibited surface CD25 expression and suppressed the elaboration of Th1 cytokines, IFN-γ, tumor necrosis factor-α (TNF-α), and IL-2 when compared with untreated MSCs (UT-MSCs). T cell suppression by MSC-17 correlated with increased IL-6 but not with indoleamine 2,3-dioxygenase 1, cyclooxygenase 1, and transforming growth factor ß-1. MSC-17 but not MSC-γ consistently induced CD4(+) CD25(high) CD127(low) FoxP3(+) regulatory T cells (iTregs) from PHA-activated CD4(+) CD25(-) T cells. MSC-induced iTregs expressed CD39, CD73, CD69, OX40, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), and glucocorticoid-induced TNFR-related protein (GITR). These suppressive MSCs-17 can engender Tregs to potently suppress T cell activation with minimal immunogenicity and thus represent a superior T cell immunomodulator for clinical application.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-17 / Células Madre Mesenquimatosas / Factores Inmunológicos Límite: Humans Idioma: En Revista: Stem Cells Año: 2015 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-17 / Células Madre Mesenquimatosas / Factores Inmunológicos Límite: Humans Idioma: En Revista: Stem Cells Año: 2015 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido