TY - JOUR
T1 - Cytokines regulate the antigen-presenting characteristics of human circulating and tissue-resident intestinal ILCs
AU - Rao, Anna
AU - Strauss, Otto
AU - Kokkinou, Efthymia
AU - Bruchard, M. lanie
AU - Tripathi, Kumar P.
AU - Schlums, Heinrich
AU - Carrasco, Anna
AU - Mazzurana, Luca
AU - Konya, Viktoria
AU - Villablanca, Eduardo J.
AU - Björkström, Niklas K.
AU - Lindforss, Ulrik
AU - Spits, Hergen
AU - Mjösberg, Jenny
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85083665873&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-020-15695-x
DO - https://doi.org/10.1038/s41467-020-15695-x
M3 - Article
C2 - 32341343
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2049
ER -