| Autor: |
África Martínez-Blanco, Marilú Domínguez-Pantoja, María Botía-Sánchez, Sonia Pérez-Cabrera, Nerea Bello-Iglesias, Paula Carrillo-Rodríguez, Natividad Martin-Morales, Antonio Lario-Simón, María M. Pérez-Sánchez-Cañete, Laura Montosa-Hidalgo, Salvador Guerrero-Fernández, Victoria M. Longobardo-Polanco, Sandra Redondo-Sánchez, Alberto Cornet-Gomez, María Torres-Sáez, Ana Fernández-Ibáñez, Laura Terrón-Camero, Eduardo Andrés-León, Francisco O’Valle, Ramón Merino, Mercedes Zubiaur, Jaime Sancho |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 12 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2021.713697 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
