Trib1 Is Overexpressed in Systemic Lupus Erythematosus, While It Regulates Immunoglobulin Production in Murine B Cells.

Fiche publication

Date publication

janvier 2018

Journal

Frontiers in immunology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr REINA-SAN-MARTIN Bernardo , Pr MARTIN Thierry

Tous les auteurs :
Simoni L, Delgado V, Ruer-Laventie J, Bouis D, Soley A, Heyer V, Robert I, Gies V, Martin T, Korganow AS, San Martin BR, Soulas-Sprauel P

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/29599769

Résumé

Systemic lupus erythematosus (SLE) is a severe and heterogeneous autoimmune disease with a complex genetic etiology, characterized by the production of various pathogenic autoantibodies, which participate in end-organ damages. The majority of human SLE occurs in adults as a polygenic disease, and clinical flares interspersed with silent phases of various lengths characterize the usual evolution of the disease in time. Trying to understand the mechanism of the different phenotypic traits of the disease, and considering the central role of B cells in SLE, we previously performed a detailed wide analysis of gene expression variation in B cells from quiescent SLE patients. This analysis pointed out an overexpression of . TRIB1 is a pseudokinase that has been implicated in the development of leukemia and also metabolic disorders. It is hypothesized that Trib1 plays an adapter or scaffold function in signaling pathways, notably in MAPK pathways. Therefore, we planned to understand the functional significance of overexpression in B cells in SLE. We produced a new knock-in model with B-cell-specific overexpression of . We showed that overexpression of specifically in B cells does not impact B cell development nor induce any development of SLE symptoms in the mice. By contrast, Trib1 has a negative regulatory function on the production of immunoglobulins, notably IgG1, but also on the production of autoantibodies in an induced model. We observed a decrease of Erk activation in BCR-stimulated overexpressing B cells. Finally, we searched for Trib1 partners in B cells by proteomic analysis in order to explore the regulatory function of Trib1 in B cells. Interestingly, we find an interaction between Trib1 and CD72, a negative regulator of B cells whose deficiency in mice leads to the development of autoimmunity. In conclusion, the overexpression of could be one of the molecular pathways implicated in the negative regulation of B cells during SLE.