期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-15695-x
关键词
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资金
- Knut and Alice Wallenberg Foundation
- Swedish Research Council
- Centre for Innovative Medicine
- Jonasson center at the Royal Institute of Technology, Sweden
- board of research at the Karolinska Institute
- research committee at the Karolinska hospital
- German Research Foundation (Deutsche Forschungsgemeinschaft) [RA 2986/1-1]
- Swedish Cancer Foundation [130396, 160664, 170082]
- Swedish Research Council [521-2013-2791]
- Swedish Society for Medical Research [4-140/2014]
- Swedish Foundation for Strategic Research [FFL15-0120]
- Knut and Alice Wallenberg Foundation [4-1198/2016]
- EMBO long-term fellowship [ALTF 786-2013]
- Karolinska Institutet
- ERC-2013-ADG [341038]
- Swedish Foundation for Strategic Research (SSF) [FFL15-0120] Funding Source: Swedish Foundation for Strategic Research (SSF)
- European Research Council (ERC) [341038] Funding Source: European Research Council (ERC)
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-1 beta and IL-18. IL-1 beta drives the expression of HLA-DR and co-stimulatory molecules on PB ILCs in an NF-kappa B-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-beta. 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.
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