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Selective impairment of TH17-differentiation and protection against autoimmune arthritis after overexpression of BCL2A1 in T lymphocytes

Abstract: The inhibition of apoptotic cell death in T cells through the dysregulated expression of BCL2 family members has been associated with the protection against the development of different autoimmune diseases. However, multiple mechanisms were proposed to be responsible for such protective effect. The purpose of this study was to explore the effect of the Tcell overexpression of BCL2A1, an anti-apoptotic BCL2 family member without an effect on cell cycle progression, in the development of collagen-induced arthritis. Our results demonstrated an attenuated development of arthritis in these transgenic mice. The protective effect was unrelated to the suppressive activity of regulatory T cells but it was associated with a defective activation of p38 mitogen-activated protein kinase in CD4+ cells after in vitro TCR stimulation. In addition, the in vitro and in vivo TH17 differentiation were impaired in BCL2A1 transgenic mice. Taken together, we demonstrated here a previously unknown role for BCL2A1 controlling the activation of CD4+ cells and their differentiation into pathogenic proinflammatory TH17 cells and identified BCL2A1 as a potential target in the control of autoimmune/inflammatory diseases.

 Fuente: PLoS One, 2016, 11(7), e0159714

 Publisher: Public Library of Science

 Year of publication: 2016

 No. of pages: 16

 Publication type: Article

 DOI: 10.1371/journal.pone.0159714

 ISSN: 1932-6203

 Publication Url: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159714

Authorship

MARCOS IGLESIAS LOZANO

AUGUSTIN RODRÍGUEZ, JUAN JESÚS

PILAR ALVAREZ SAINZ DE LA MAZA

INES SANTIUSTE TORCIDA

JORGE POSTIGO FERNANDEZ