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The cytokine receptor DR3 identifies and promotes the activation of thymic NKT17 cells

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Abstract

Invariant natural killer T (iNKT) cells correspond to a population of thymus-generated T cells with innate-like characteristics and effector functions. Among the various iNKT subsets, NKT17 is the only subset that produces the proinflammatory cytokine IL-17. But, how NKT17 cells acquire this ability and what would selectively trigger their activation remain incompletely understood. Here, we identified the cytokine receptor DR3 being specifically expressed on thymic NKT17 cells and mostly absent on other thymic iNKT subsets. Moreover, DR3 ligation promoted the in vivo activation of thymic NKT17 cells and provided costimulatory effects upon agonistic α-GalCer stimulation. Thus, we identified a specific surface marker for thymic NKT17 cells that triggers their activation and augments their effector functions both in vivo and in vitro. These findings provide new insights for deciphering the role and function of murine NKT17 cells and for understanding the development and activation mechanisms of iNKT cells in general.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Acknowledgements

We thank Joo-Young Park (Seoul National University) for the critical review of the manuscript. We are also grateful for members of the EIB FACS core facility for their help and expertise in flow cytometry data acquisition and analyses.

Funding

This study has been supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research.

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Author notes

  1. Shunqun Luo and Nurcin Liman have contributed equally.

Authors and Affiliations

  1. Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Building 10, Room 5B17, 10 Center Dr, Bethesda, MD, 20892, USA

    Shunqun Luo, Nurcin Liman, Can Li, Assiatu Crossman & Jung-Hyun Park

  2. Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK

    Eddie C. Y. Wang

  3. Translational Immunology Section, NIAMS, NIH, Bethesda, MD, 20892, USA

    Françoise Meylan

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  1. Shunqun Luo
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Contributions

SL and NL: designed and performed the experiments, analyzed the data, and contributed to the writing of the manuscript. CL and AC: performed experiments, analyzed the data, and commented on the manuscript. EW and FM: provided reagents, experimental expertise, and edited the manuscript. JP: conceived the project, analyzed the data, and wrote the manuscript.

Corresponding author

Correspondence to Jung-Hyun Park.

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The authors declare that they have no conflict of interest.

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All animal procedures reported in this study that were performed by NCI-CCR affiliated staff were approved by the NCI Animal Care and Use Committee (ACUC) and in accordance with federal regulatory requirements and standards. All components of the intramural NIH ACU program are accredited by AAALAC International. All mice were cared for in accordance with the Public Health Service policy on human care and use of laboratory animals and NIH guidelines.

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Luo, S., Liman, N., Li, C. et al. The cytokine receptor DR3 identifies and promotes the activation of thymic NKT17 cells. Cell. Mol. Life Sci. 80, 76 (2023). https://doi.org/10.1007/s00018-023-04726-7

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  • DOI: https://doi.org/10.1007/s00018-023-04726-7

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