Inflammatory conditions dictate the effect of Mesenchymal stem or Stromal cells on B cell function
Luk, Franka (Erasmus University Medical Center, Rotterdam)
Carreras-Planella, Laura (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Korevaar, Sander S. (Erasmus University Medical Center, Rotterdam)
de Witte, Samantha F. H. (Erasmus University Medical Center, Rotterdam)
Borràs i Serres, Francesc Enric (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Betjes, Michiel G. H. (Erasmus University Medical Center, Rotterdam)
Baan, Carla C. (Erasmus University Medical Center, Rotterdam)
Hoogduijn, Martin J. (Erasmus University Medical Center, Rotterdam)
Franquesa, Marcella (Erasmus University Medical Center, Rotterdam)

Data:	2017
Resum:	The immunomodulatory capacity of mesenchymal stem or stromal cells (MSC) makes them a promising tool for treatment of immune disease and organ transplantation. The effects of MSC on B cells are characterized by an abrogation of plasmablast formation and induction of regulatory B cells (Bregs). It is, however, unknown how MSC interact with B cells under inflammatory conditions. In this study, adipose tissue-derived MSC were pretreated with 50 ng/ml IFN-γ for 96 h (MSC-IFN-γ) to simulate inflammatory conditions. Mature B cells were obtained from spleens by CD43− selection. B cells were co-cultured with MSC and stimulated with anti-IgM, anti-CD40, and IL-2; and after 7 days, B cell proliferation, phenotype, Immunoglobulin-G (IgG), and IL-10 production were analyzed. MSC did not inhibit B cell proliferation but increased the percentage of CD38high CD24high B cells (Bregs) and IL-10 production, while MSC-IFN-γ significantly reduced B cell proliferation and inhibited IgG production by B cells in a more potent fashion but did not induce Bregs or IL-10 production. Both MSC and MSC-IFN-γ required proximity to target cells and being metabolically active to exert their effects. Indoleamine 2,3 dioxygenase expression was highly induced in MSC-IFN-γ and was responsible of the anti-proliferative and Breg reduction since addition of tryptophan (TRP) restored MSC properties. Immunological conditions dictate the effect of MSC on B cell function. Under immunological quiescent conditions, MSC stimulate Breg induction; whereas, under inflammatory conditions, MSC inhibit B cell proliferation and maturation through depletion of TRP. This knowledge is useful for customizing MSC therapy for specific purposes by appropriate pretreatment of MSC.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2014BP B00118
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	B cell ; Immunomodulation ; Mesenchymal stem cell ; Plasmablast ; Regulatory B cell ; Indoleamine ; 2,3-dioxygenase
Publicat a:	Frontiers in immunology, Vol. 8 (august 2017) , p. 1-13, ISSN 1664-3224

DOI: 10.3389/fimmu.2017.01042
PMID: 28894451

13 p, 6.6 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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