PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and...

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Detalles Bibliográficos
Autores: Tchen, John, Simon, Quentin|||0000-0002-2383-2809, Chapart, Léa|||0009-0008-9720-1146, Thaminy, Morgane K.|||0009-0002-4842-0277, Vibhushan, Shamila|||0000-0001-6196-2295, Saveanu, Loredana|||0000-0003-3138-7968, Lamri, Yasmine, Saidoune, Fanny, Pacreau, Emeline, Pellefigues, Christophe|||0000-0001-7036-0763, Bex-coudrat, Julie, Karasuyama, Hajime|||0000-0003-0689-0836, Miyake, Kensuke|||0000-0003-1149-3755, Hidalgo Pareja, Juan|||0000-0003-0921-1122, Fallon, Padraic G.|||0000-0002-8401-7293, Papo, Thomas, Blank, Ulrich|||0000-0002-2661-2983, Benhamou, Marc, Hanouna, Guillaume, Sacre, Karim|||0000-0002-6544-234X, Daugas, Eric, Charles, Nicolas|||0000-0002-5416-5834
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:310540
Acceso en línea:https://ddd.uab.cat/record/310540
https://dx.doi.org/urn:doi:10.1038/s41467-024-47691-w
Access Level:acceso abierto
Palabra clave:Autoimmunity
Basophils
Translational immunology
Lupus nephritis
Germinal centres
Descripción
Sumario:Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms that remain to be defined. Here, we provide evidence for a direct functional relationship between TFH cells and basophils during lupus pathogenesis, both in humans and mice. PD-L1 upregulation on basophils and IL-4 production are associated with TFH and TFH2 cell expansions and with disease activity. Pathogenic TFH cell accumulation, maintenance, and function in SLO were dependent on PD-L1 and IL-4 in basophils, which induced a transcriptional program allowing TFH2 cell differentiation and function. Our study establishes a direct mechanistic link between basophils and TFH cells in SLE that promotes autoantibody production and lupus nephritis.

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