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

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.

SUBMITTER: Rao A

PROVIDER: S-EPMC7184749 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-02 | GSE147908 | GEO

Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [II]

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Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses [I]

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