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

Tchen, J.; SIMON, Q.; CHAPART, L.; LAMRI, Y.; SAIDOUNE, F.; PACREAU, E.; PELLEFIGUES, C.; BEX-COUDRAT, J.; KARASUYAMA, H.; MIYAKE, K.; Hidalgo, J.; Fallon, P. G.; PAPO, T.; BLANK, U.; BENHAMOU, M.; HANOUNA, G.; SACRE, K.; DAUGAS, E.; CHARLES, N.

2023-01-11 allergy and immunology
10.1101/2023.01.10.23284399 medRxiv
Show abstract

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.

Published in Nature Communications (predicted rank #2) · training set

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