Cytokines regulate the antigen-presenting characteristics of human circulating and tissue-resident intestinal ILCs

Anna Rao (), Otto Strauss, Efthymia Kokkinou, Mélanie Bruchard, Kumar P. Tripathi, Heinrich Schlums, Anna Carrasco, Luca Mazzurana, Viktoria Konya, Eduardo J. Villablanca, Niklas K. Björkström, Ulrik Lindforss, Hergen Spits and Jenny Mjösberg ()
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Anna Rao: Karolinska University Hospital Huddinge
Otto Strauss: Karolinska University Hospital Huddinge
Efthymia Kokkinou: Karolinska University Hospital Huddinge
Mélanie Bruchard: Academic Medical Center at the University of Amsterdam
Kumar P. Tripathi: Karolinska Institutet and Karolinska University Hospital
Heinrich Schlums: Karolinska Institutet
Anna Carrasco: Karolinska University Hospital Huddinge
Luca Mazzurana: Karolinska University Hospital Huddinge
Viktoria Konya: Karolinska University Hospital Huddinge
Eduardo J. Villablanca: Karolinska Institutet and Karolinska University Hospital
Niklas K. Björkström: Karolinska University Hospital Huddinge
Ulrik Lindforss: Karolinska University Hospital
Hergen Spits: Academic Medical Center at the University of Amsterdam
Jenny Mjösberg: Karolinska University Hospital Huddinge

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15695-x

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