Role of interleukin-1ß in the regulation of T cell- mediated humoral responses - Sorbonne Université Access content directly
Conference Poster Year : 2022

Role of interleukin-1ß in the regulation of T cell- mediated humoral responses

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 humoral responses in humans. Methods: To uncover the role of IL-1ß in the regulation of TFOL activation within lymphoid organs, we submitted human tonsil cell suspensions to pan-lymphocyte stimulation via CD3/CD28 beads, either in bulk or sorted CXCR5+ TFOL only, and we cultured the cells with different concentrations of IL-1ß. We followed T and B cell phenotype over time through high-dimensional cytometry analysis. In addition, we explored a cohort of untreated autoimmune patients through transcriptomic and cytometry analysis of circulating TFOL seek for IL-1ß involvement in disease physiopathology. Results: Our observations first indicate that IL-1 receptors, IL-1R1 and IL-1R2, have a differential expression among T cell subsets and are modulated over time following activation and IL-1β exposure. IL-1β enhances B cell survival and activation, while its impact on TFOL activation is more heterogenous and dose-dependent. Plus, our findings highlight an IL-1β signature in some autoimmune pathologies, for which we seek to find correlations with TFH/TFR disruption. Conclusion: In sum, our results point out that IL-1β has a direct impact on the key players of the humoral response, namely GC B cells and TFOL. While these mechanisms need to be described more thoroughly, they will help better understand antibody-driven autoimmune physiopathology.
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Dates and versions

hal-03994997 , version 1 (17-02-2023)

Identifiers

  • HAL Id : hal-03994997 , version 1

Cite

Romain Vaineau, Samir Ali-Moussa, David Klatzmann, Nicolas Tchitchek, Stéphanie Graff-Dubois. Role of interleukin-1ß in the regulation of T cell- mediated humoral responses. Joint Annual Meetings of the French Society for Immunology (SFI) and the French Cytometry Association (AFC), Nov 2022, Nice, France. ⟨hal-03994997⟩
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