title: 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 T-cell 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.
authors.affiliation: Departamento de Biología Molecular-IDIVAL Universidad de Cantabria, Santander, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Iglesias
authors.affiliation: Departamento de Biología Molecular-IDIVAL Universidad de Cantabria, Santander, Spain.|Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas-Universidad de Cantabria, Santander, Spain.
authors.forename: Juan Jesús
authors.initials: JJ
authors.lastname: Augustin
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas-Universidad de Cantabria, Santander, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Alvarez
authors.affiliation: Departamento de Biología Molecular-IDIVAL Universidad de Cantabria, Santander, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Santiuste
authors.affiliation: Departamento de Biología Molecular-IDIVAL Universidad de Cantabria, Santander, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Postigo
authors.affiliation: Departamento de Biología Molecular-IDIVAL Universidad de Cantabria, Santander, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Merino
authors.affiliation: Departamento de Biología Molecular-IDIVAL Universidad de Cantabria, Santander, Spain.|Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas-Universidad de Cantabria, Santander, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Merino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D065840:Protective Factors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: C096816:BCL2-related protein A1; D015704:CD4 Antigens; D016207:Cytokines; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D048051:p38 Mitogen-Activated Protein Kinases