Dendritic and stromal cells from the spleen of lupic mice present phenotypic and functional abnormalities |
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| Institution: | 1. Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile;2. Facultad de Ciencias de la Salud, Universidad Andres Bello, Santiago, Chile;3. Fundacion Ciencia & Vida, Santiago, Chile;1. Cirugía Hepatobiliopancreática y Trasplante Hepático y Pancreático, Instituto de Enfermedades Metabólicas y Digestivas, Hospital Clínic, Universidad de Barcelona, Barcelona, España;2. Unidad de Trasplante Renal, Servicio de Nefrología y Trasplante Renal, Hospital Clínic, Barcelona, España;3. Servicio de Radiología, Centro de Diagnóstico por la Imagen, Hospital Clínic, Barcelona, España;4. Unidad de Diabetes, Servicio de Endocrinología y Nutrición, Instituto de Enfermedades Metabólicas y Digestivas, Hospital Clínic, Barcelona, España;1. Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;2. Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy;1. AP-HP, Cochin Hospital, Internal Medicine Department, Centre de référence maladies auto-immunes et systémiques rares, 75014 Paris, France;2. Université Paris Descartes-Sorbonne Paris Cité, Paris, France;3. INSERM U 1153, Center for Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France;4. Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium;5. Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Université Catholique de Louvain, Brussels, Belgium |
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| Abstract: | Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the increase in the percentage of autoreactive B and T lymphocytes. Since dendritic cells (DCs) are essential for B cell and T cell function, we hypothesized that changes in DC biology may play a critical role in the pathogenesis of the disease. We analyzed the phenotype and distribution of two main DC subsets, conventional (cDC) and plasmacytoid (pDC), in lupus prone (NZW×NZB)F1 (BWF1) mice and age-matched NZW×BALB/c control mice. Our results show that both subsets of lupic DCs displayed an abnormal phenotype, characterized by an over-expression of the co-stimulatory molecules CD80, CD86, PD-L1 and PD-L2 compared with control mice. Accordingly, spleen CD4+ T cells from lupic mice exhibit an activated phenotype characterized by a higher expression of PD-1, CD25, CD69 and increased secretion of IFN-γ and IL-10. Interestingly, lupic mice also present an increase in the percentage of cDC in peripheral blood and an increase in the percentage of pDCs in spleen and mesenteric lymph nodes (MLNs) compared with control and pre-lupic mice. Homing experiments demonstrate that lupic and pre-lupic DCs migrate preferentially to the spleen compared to DCs from control mice. This preferential recruitment and retention of DCs in the spleen is related to an altered expression of different chemokine and chemokine receptors on both, DCs and stromal cells from lupic mice. Our results suggest that this altered phenotype and migratory behavior shown by DCs from lupic mice may account for the abnormal T cell and B cell responses in lupus. |
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