Article Text

other Versions

PDF
Human adipose-derived mesenchymal stem cells reduce inflammatory and T-cell responses and induce regulatory T cells in vitro in rheumatoid arthritis
  1. Elena Gonzalez-Rey (elenag{at}ipb.csic.es)
  1. School of Medicine, Seville University, Seville, Spain
    1. Manuel A Gonzalez
    1. Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain
      1. Nieves Varela
      1. Instituto de Parasitologia y Biomedicina, CSIC, Granada, Spain
        1. Francisco O'Valle
        1. School of Medicine, University of Granada, Spain
          1. Pedro Hernandez-Cortes
          1. San Cecilio University Hospital, Spain
            1. Laura Rico
            1. Cellerix, SA, Madrid, Spain
              1. Dirk Büscher
              1. Cellerix, SA, Madrid, Spain
                1. Mario Delgado (mdelgado{at}ipb.csic.es)
                1. Instituto de Parasitologia y Biomedicina, CSIC, Granada, Spain

                  Abstract

                  Objectives: Adult mesenchymal stem cells were recently found to suppress effector T-cell and inflammatory responses and have emerged as attractive therapeutic candidates for immune disorders. In rheumatoid arthritis (RA), a loss in the immunological self-tolerance causes the activation of autorreactive T cells against joint components and subsequent chronic inflammation. The aim of this study is to characterize the immunosuppresive activity of human adipose-derived mesenchymal stem cells (hASCs) on collagen-reactive T cells from RA patients.

                  Methods: We investigated the effects of hASCs on collagen-reactive RA human T-cell proliferation and cytokine production, as well as on the production of inflammatory mediators by monocytes and fibroblast-like synoviocytes from RA patients.

                  Results: hASCs suppressed antigen-specific response of T cells from RA patients. hASCs inhibited the proliferative response and the production of inflammatory cytokines by collagen-activated CD4 and CD8 T cells. In contrast, the number of IL-10-producing T cells and monocytes significantly augmented upon hASC-treatment. The suppressive activity of hASCs was both cell-to-cell contact-dependent and -independent. hASCs also stimulated the generation of FoxP3-expressing CD4+CD25+ regulatory T cells with capacity to suppress collagen-specific T-cell responses. Finally, hASCs donwregulated the inflammatory response and the production of matrix-degrading enzymes by synovial cells isolated from RA patients.

                  Conclusions: Our work identifies to hASCs as key regulators of immune tolerance with capacity to suppress T-cell and inflammatory responses to induce the generation/activation of antigen-specific regulatory T cells.

                  Statistics from Altmetric.com

                  Request permissions

                  If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.