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CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism
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-H...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421681/ https://www.ncbi.nlm.nih.gov/pubmed/34504495 http://dx.doi.org/10.3389/fimmu.2021.713697 |
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author | Martínez-Blanco, África Domínguez-Pantoja, Marilú Botía-Sánchez, María Pérez-Cabrera, Sonia Bello-Iglesias, Nerea Carrillo-Rodríguez, Paula Martin-Morales, Natividad Lario-Simón, Antonio Pérez-Sánchez-Cañete, María M. Montosa-Hidalgo, Laura Guerrero-Fernández, Salvador Longobardo-Polanco, Victoria M. Redondo-Sánchez, Sandra Cornet-Gomez, Alberto Torres-Sáez, María Fernández-Ibáñez, Ana Terrón-Camero, Laura Andrés-León, Eduardo O’Valle, Francisco Merino, Ramón Zubiaur, Mercedes Sancho, Jaime |
author_facet | Martínez-Blanco, África Domínguez-Pantoja, Marilú Botía-Sánchez, María Pérez-Cabrera, Sonia Bello-Iglesias, Nerea Carrillo-Rodríguez, Paula Martin-Morales, Natividad Lario-Simón, Antonio Pérez-Sánchez-Cañete, María M. Montosa-Hidalgo, Laura Guerrero-Fernández, Salvador Longobardo-Polanco, Victoria M. Redondo-Sánchez, Sandra Cornet-Gomez, Alberto Torres-Sáez, María Fernández-Ibáñez, Ana Terrón-Camero, Laura Andrés-León, Eduardo O’Valle, Francisco Merino, Ramón Zubiaur, Mercedes Sancho, Jaime |
author_sort | Martínez-Blanco, África |
collection | PubMed |
description | 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(+)CD11c(hi) 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(+)CD11c(hi) 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. |
format | Online Article Text |
id | pubmed-8421681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84216812021-09-08 CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism Martínez-Blanco, África Domínguez-Pantoja, Marilú Botía-Sánchez, María Pérez-Cabrera, Sonia Bello-Iglesias, Nerea Carrillo-Rodríguez, Paula Martin-Morales, Natividad Lario-Simón, Antonio Pérez-Sánchez-Cañete, María M. Montosa-Hidalgo, Laura Guerrero-Fernández, Salvador Longobardo-Polanco, Victoria M. Redondo-Sánchez, Sandra Cornet-Gomez, Alberto Torres-Sáez, María Fernández-Ibáñez, Ana Terrón-Camero, Laura Andrés-León, Eduardo O’Valle, Francisco Merino, Ramón Zubiaur, Mercedes Sancho, Jaime Front Immunol Immunology 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(+)CD11c(hi) 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(+)CD11c(hi) 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. Frontiers Media S.A. 2021-08-24 /pmc/articles/PMC8421681/ /pubmed/34504495 http://dx.doi.org/10.3389/fimmu.2021.713697 Text en Copyright © 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 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Martínez-Blanco, África Domínguez-Pantoja, Marilú Botía-Sánchez, María Pérez-Cabrera, Sonia Bello-Iglesias, Nerea Carrillo-Rodríguez, Paula Martin-Morales, Natividad Lario-Simón, Antonio Pérez-Sánchez-Cañete, María M. Montosa-Hidalgo, Laura Guerrero-Fernández, Salvador Longobardo-Polanco, Victoria M. Redondo-Sánchez, Sandra Cornet-Gomez, Alberto Torres-Sáez, María Fernández-Ibáñez, Ana Terrón-Camero, Laura Andrés-León, Eduardo O’Valle, Francisco Merino, Ramón Zubiaur, Mercedes Sancho, Jaime CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism |
title | CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism |
title_full | CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism |
title_fullStr | CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism |
title_full_unstemmed | CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism |
title_short | CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism |
title_sort | cd38 deficiency ameliorates chronic graft-versus-host disease murine lupus via a b-cell-dependent mechanism |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421681/ https://www.ncbi.nlm.nih.gov/pubmed/34504495 http://dx.doi.org/10.3389/fimmu.2021.713697 |
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