Fiche publication
Date publication
avril 2020
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRUCHARD Mélanie
Tous les auteurs :
Rao A, Strauss O, Kokkinou E, Bruchard M, Tripathi KP, Schlums H, Carrasco A, Mazzurana L, Konya V, Villablanca EJ, Björkström NK, Lindforss U, Spits H, Mjösberg J
Lien Pubmed
Résumé
ILCs and T helper cells have been shown to exert bi-directional regulation in mice. However, how crosstalk between ILCs and CD4 T cells influences immune function in humans is unknown. Here we show that human intestinal ILCs co-localize with T cells in healthy and colorectal cancer tissue and display elevated HLA-DR expression in tumor and tumor-adjacent areas. Although mostly lacking co-stimulatory molecules ex vivo, intestinal and peripheral blood (PB) ILCs acquire antigen-presenting characteristics triggered by inflammasome-associated cytokines IL-1β and IL-18. IL-1β drives the expression of HLA-DR and co-stimulatory molecules on PB ILCs in an NF-κB-dependent manner, priming them as efficient inducers of cytomegalovirus-specific memory CD4 T-cell responses. This effect is strongly inhibited by the anti-inflammatory cytokine TGF-β. Our results suggest that circulating and tissue-resident ILCs have the intrinsic capacity to respond to the immediate cytokine milieu and regulate local CD4 T-cell responses, with potential implications for anti-tumor immunity and inflammation.
Référence
Nat Commun. 2020 Apr 27;11(1):2049
