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Título: | CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism |
Autor: | Martínez Blanco, África; Domínguez-Pantoja, Marilú; Botía Sánchez, María; Pérez Cabrera, Sonia; Bello Iglesias, Nerea; Carrillo Rodríguez, Paula; Martin-Morales, Natividad; Lario, Antonio; Pérez-Sánchez-Cañete, María M.; Montosa, Laura; Guerrero, Salvador; Longobardo, Victoria; Redondo-Sánchez, Sandra; Cornet-Gomez, Alberto; Torres Sáez, María; Fernández-Ibáñez, Ana; Terrón-Camero, Laura Carmen CSIC ORCID; Andrés-León, Eduardo CSIC ORCID CVN ; O’Valle, Francisco; Merino, Ramón CSIC ORCID | Palabras clave: | CD38 cGVHD lupus-like T-bet+ B cells Anti-ssDNA antibodies GC B cells STAT1 Type I IFN-signature Inflammation |
Fecha de publicación: | ago-2021 | Editor: | Frontiers Media | Citación: | Frontiers in Immunology 12: 713697 (2021) | Resumen: | The absence of the mouse cell surface receptor CD38 in Cd38−/− mice suggests that this receptor acts as a positive regulator of inflammatory and autoimmune responses. Here, we report that, in the context of the chronic graft-versus-host disease (cGVHD) lupus inducible model, the transfer of B6.C-H2bm12/KhEg(bm12) spleen cells into co-isogenic Cd38−/− B6 mice causes milder lupus-like autoimmunity with lower levels of anti-ssDNA autoantibodies than the transfer of bm12 spleen cells into WT B6 mice. In addition, significantly lower percentages of Tfh cells, as well as GC B cells, plasma cells, and T-bet+CD11chi B cells, were observed in Cd38−/− mice than in WT mice, while the expansion of Treg cells and Tfr cells was normal, suggesting that the ability of Cd38−/− B cells to respond to allogeneic help from bm12 CD4+ T cells is greatly diminished. The frequencies of T-bet+CD11chi B cells, which are considered the precursors of the autoantibody-secreting cells, correlate with anti-ssDNA autoantibody serum levels, IL-27, and sCD40L. Proteomics profiling of the spleens from WT cGVHD mice reflects a STAT1-driven type I IFN signature, which is absent in Cd38−/− cGVHD mice. Kidney, spleen, and liver inflammation was mild and resolved faster in Cd38−/− cGVHD mice than in WT cGVHD mice. We conclude that CD38 in B cells functions as a modulator receptor that controls autoimmune responses. | Descripción: | © 2021 Martínez-Blanco, Domínguez-Pantoja, Botía-Sánchez, Pérez-Cabrera, Bello-Iglesias, Carrillo-Rodríguez, Martin-Morales, Lario-Simón, Pérez-Sánchez-Cañete, Montosa-Hidalgo, Guerrero-Fernández, Longobardo-Polanco, Redondo-Sánchez, Cornet-Gomez, Torres-Sáez, Fernández-Ibáñez, Terrón-Camero, Andrés-León, O’Valle, Merino, Zubiaur and Sancho. | Versión del editor: | http://dx.doi.org/10.3389/fimmu.2021.713697 | URI: | http://hdl.handle.net/10261/262459 | DOI: | 10.3389/fimmu.2021.713697 | E-ISSN: | 1664-3224 |
Aparece en las colecciones: | (IBBTEC) Artículos (IPBLN) Artículos |
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CD38 Deficiency Ameliorates_Martínez_PV_Art2021.pdf | 16,7 MB | Adobe PDF | Visualizar/Abrir |
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