Pathogenic accumulation of T follicular helper cells in lupus disease depends on PD-L1 and IL-4 expressing basophils

Autor: John Tchen, Quentin Simon, Léa Chapart, Yasmine Lamri, Fanny Saidoune, Emeline Pacreau, Christophe Pellefigues, Julie Bex-Coudrat, Hajime Karasuyama, Kensuke Miyake, Juan Hidalgo, Padraic G. Fallon, Thomas Papo, Ulrich Blank, Marc Benhamou, Guillaume Hanouna, Karim Sacre, Eric Daugas, Nicolas Charles
Rok vydání: 2023
Popis: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies raised against nuclear antigens and whose production is promoted by autoreactive T follicular helper (TFH) cells. Basophils, by accumulating in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms to be defined. Here, we demonstrate that a functional relationship between TFH cells and basophils occurs in SLO during lupus pathogenesis. On SLE patient blood basophils, PD-L1 expression was upregulated and associated with TFH and TFH2 cell expansions and with disease activity. In two distinct lupus-like mouse models, TFH cell pathogenic accumulation, maintenance and function, and disease activity were dependent on basophils and their expressions of PD-L1 and IL-4. Our study establishes a direct link between basophils and TFH cells in the SLE context that promotes autoreactive IgG production and lupus nephritis pathogenesis. Altering the basophil/TFH cell axis in the SLE context may represent a promising innovative intervention strategy in SLE.
Databáze: OpenAIRE