Cd38 deficiency ameliorates chronic graft versus Host disease murine lupus via a b-cell dependent mechanism

Trabajo presentado en el II Congreso investigación PTS, celebrado en Granada (España) del 09 al 11 de febrero de 2022.Absence of mouse cell surface receptor CD38 in Cd38-/- mice suggests that this receptor acts as positive regulator of inflammatory and autoimmune responses. Here we report that in the setting of a chronic graft versus host disease (cGVHD) lupus model induced by 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. I In addition, significantly lower percentages of Tfh cells, as well as GC B cells, plasma cells and T-bet+CD11chi B cells are observed in Cd38-/- mice than in WT mice, while the expansion of Treg cells, and Tfr cells is 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, with IL-27, and sCD40L. Proteomics profiling of 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 in B cells CD38 functions as a modulator receptor that controls autoimmune responses

Proteomics analyses of Extracellular Vesicles from peritoneal exudates reveal the elicited inflammatory/autoimmune response in the chronic graft versus host disease lupus model.

Congresos y Conferencias: Comunicación de Congreso - Conferencia invitada.Systemic Lupus Erythematous (SLE) is a complex autoimmune disease, characterized by increased cellular death by apoptosis and defective clearance of apoptotic bodies and nuclear fragments, resulting in increased antinuclear antibody production. We have used the inducible bm12 lupus model, where an abnormal chronic graft versus host disease (cGvHD) is induced in non-autoimmune C57BL6 mice (WT) by the adoptive transfer of MHC Class II IA-incompatible bm12 spleen cells. In the absence of CD38 in the host (CD38KO mice), we have observed a significant decrease in the severity of the disease (doi: 10.3389/fimmu.2021.713697). Objectives: Analyze the protein composition and function of EVs released in the peritoneal cavity of cGvHD mice, to identify predictive or diagnostic biomarkers of the disease Methods: EVs were isolated by qEV size-exclusion-chromatography (SEC) from peritoneal exudates of cGVHD lupus-mice, two weeks after the adoptive transfer of bm12 cells. Protein extracts from isolated EVs were analyzed by LC-MS/MS. Protein identification was performed with ProteinScape, and MASCOT data searching using Swiss-Prot database. To quantify protein abundance, the emPAI-based method was used. We used ClueGO and CluePedia apps within the Cytoscape software for functional analysis