Dendritic and stromal cells from the spleen of lupic mice present phenotypic and functional abnormalities
Author
dc.contributor.author
Gleisner, Maria Alejandra
Author
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Reyes, Paz
es_CL
Author
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Alfaro, Jennifer
es_CL
Author
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Solanes, Paola
es_CL
Author
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Simon, Valeska
es_CL
Author
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Crisostomo, Natalia
es_CL
Author
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Sauma Mahaluf, Daniela
es_CL
Author
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Rosemblatt Silber, Mario César
es_CL
Author
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Bono Merino, María Rosa
es_CL
Admission date
dc.date.accessioned
2014-01-28T13:57:52Z
Available date
dc.date.available
2014-01-28T13:57:52Z
Publication date
dc.date.issued
2013
Cita de ítem
dc.identifier.citation
Molecular Immunology 54 (2013) 423– 434
en_US
Identifier
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DOI: 10.1016/j.molimm.2013.01.011
Identifier
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https://repositorio.uchile.cl/handle/2250/119718
General note
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Artículo de publicación ISI
en_US
Abstract
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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- 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.