Impact of IL-1ß on the Tfh/Tfr interplay in antibody production in humans - Sorbonne Université Access content directly
Conference Poster Year : 2021

Impact of IL-1ß on the Tfh/Tfr interplay in antibody production in humans

Impact de l'IL-1ß sur la balance Tfh/Tfr dans la production d'anticorps chez l'humain

Abstract

Objective: Antibody production is elicited by follicular helper T cells (TFH) and dampened by follicular regulatory T cells (TFR) within germinal centers (GC). We and others evidenced that the pro-inflammatory cytokine interleukin-1ß (IL-1ß) is involved in antibody production using in vivo and in vitro murine models. Given the difficult access to lymphoid-resident follicular T cells (TFOL) in humans and their scarcity in the blood, the impact of IL-1ß on TFH and TFR remains to be addressed. Here, we aim to understand the involvement of the TFH/TFR/IL-1ß interplay in physiological and pathological antibody production in humans. Methods: We explored a cohort of untreated autoimmune patients through transcriptomic analysis of circulating TFOL. Also, we developed a human lymphoid cell stimulation model that induces Tfh and Tfr allowing their functional and kinetic characterization. Hence, we assessed ex vivo and induced TFH and TFR from healthy lymphoid organs using mass cytometry and multiparameter flow cytometry. Results: Our findings highlight an IL-1β signature comprising IL-1ß sensing and signaling in multiple pathologies, which we propose to compare with TFH and TFR gene modules to identify potential correlations and target a specific autoimmune disease. In addition, our observations indicate that the receptor IL-1R1 is mainly expressed by TFR cells, but varies following the helper or regulatory profile, and upon the activation or resting phenotype of TFOL. In turn, the decoy receptor IL-1R2 displays a more heterogeneous expression. We propose to study how IL-1ß modulates TFOL kinetics upon antigenic stimulation, given their differential expression of IL-1 receptors. Conclusion: Taken together, our results may uncover the role of IL-1ß in T cell-dependent antibody production, paving the way for a better comprehension of autoimmune physiopathology.
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Dates and versions

hal-03994946 , version 1 (17-02-2023)

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  • HAL Id : hal-03994946 , version 1

Cite

Romain Vaineau, Raphael Jeger-Madiot, Aude Belbézier, Paul Engeroff, Eric Savier, et al.. Impact of IL-1ß on the Tfh/Tfr interplay in antibody production in humans. 53rd Annual Meeting of the French Society for Immunology, Dec 2021, Paris, France. ⟨hal-03994946⟩
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