Journal Article

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

Schlums, Heinrich, Strauss, Otto, Kokkinou, Efthymia, Carrasco, Anna, Villablanca, Eduardo J., Björkström, Niklas K., Mjösberg, Jenny, Konya, Viktoria, Lindforss, Ulrik, Tripathi, Kumar P., Spits, Hergen, Mazzurana, Luca, Rao, Anna, Bruchard, Mélanie

2020

Overview

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. Murine ILCs can modulate T cell responses in MHCII-dependent manner. Here the authors show that human ILCs process and present antigens and induce T-cell responses upon exposure to IL-1-family cytokines; along with the article by Lehmann et al, this work elucidates how cytokines set context specificity of ILC-T cell crosstalk by regulating ILC antigen presentation.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/21 / 13/31 / 14/19 / 38/61 / 631/250/21/1293 / 631/250/2504/2506 / 631/250/347 / 692/4020/1503/1504/1885/1393 / Animals / Antigen Presentation / Antigen-Presenting Cells - immunology / Antigens / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / Colonic Neoplasms - immunology / Colorectal cancer / Crosstalk / Cytokines / Cytokines - immunology / Helper cells / Histocompatibility antigen HLA / Humanities and Social Sciences / Humans / IL-1β / Immune response / Immunity, Innate / Immunological memory / Inflammasomes / Inflammasomes - immunology / Inflammation / Interleukin 1 / Interleukin 18 / Interleukin-18 - immunology / Interleukin-1beta - immunology / Intestinal Mucosa - immunology / Intestinal Mucosa - pathology / Intestine / Leukocytes, Mononuclear - immunology / Lymphocytes / Lymphocytes - immunology / Lymphocytes T / Mice / multidisciplinary / NF-κB protein / Peripheral blood / Priming / Science / Science (multidisciplinary)