AUTHOR=Belbezier Aude , Engeroff Paul , Fourcade Gwladys , Vantomme Hélène , Vaineau Romain , Gouritin Bruno , Bellier Bertrand , Brocheriou Isabelle , Tchitchek Nicolas , Graff-Dubois Stephanie , Klatzmann David 

TITLE=Interleukin-1 regulates follicular T cells during the germinal center reaction

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1393096

DOI=10.3389/fimmu.2024.1393096

ISSN=1664-3224

ABSTRACT=To study the role of IL-1 receptors in the regulation of the B cell response by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, we generated mice with IL-1 receptors inactivated in these cells and measured antibody production and cell activation upon immunization. While IL-1β concentration is increased in the draining lymph node after immunization, antigenspecific antibody levels and cell phenotypes indicated that IL-1β can activate both Tfh and Tfr cells through IL-1R1 stimulation. Surprisingly, IL-1R2 and IL-1Ra expression on Tfr cells does not block IL-1 activation of Tfh cells, but rather prevents IL-1/IL-1R1-mediated early activation of Tfr cells. IL-1Rs similarly regulate antibody response against autoantigens and its related pathophysiology in an experimental lupus model. Altogether, these results show that IL-1 inhibitory receptors expressed by Tfr cells prevent their own activation and suppressive function, thus licensing IL-1-mediated activation of Tfh cells after immunization.