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CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism

Authors :
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
Source :
Frontiers in Immunology, Vol 12 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

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.

Details

Language :
English
ISSN :
16643224
Volume :
12
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.00bd329d702410b9ebcd3e172e7f1ee
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2021.713697