Signature cytokine-associated transcriptome analysis of effector γδ T cells identifies subset-specific regulators of peripheral activation
γδ T cells producing either interleukin-17A (γδ<sup>17</sup> cells) or interferon-γ (γδ<sup>IFN</sup> cells) are generated in the mouse thymus, but the molecular regulators of their peripheral functions are not fully characterized. Here we established an Il17a-GFP:Ifng-YFP double-reporter mouse strain to analyze at unprecedented depth the transcriptomes of pure γδ<sup>17</sup> cell versus γδ<sup>IFN</sup> cell populations from peripheral lymph nodes. Within a very high fraction of differentially expressed genes, we identify a panel of 20 new signature genes in steady-state γδ<sup>17</sup> cells versus γδ<sup>IFN</sup> cells, which we further validate in models of experimental autoimmune encephalomyelitis and cerebral malaria, respectively. Among the signature genes, we show that the co-receptor CD6 and the signaling protein Themis promote the activation and proliferation of peripheral γδ<sup>IFN</sup> cells in response to T cell antigen receptor stimulation in vitro and to Plasmodium infection in vivo. This resource can help to understand the distinct activities of effector γδ T cell subsets in pathophysiology.
Authors
- Rita F. Santos (ORCID: https://orcid.org/0000-0003-0139-0285)
- Tiago Amado (ORCID: https://orcid.org/0000-0002-3084-6643)
- Nelly Rouquié (ORCID: https://orcid.org/0000-0002-2347-9160)
- Renaud Lesourne (ORCID: https://orcid.org/0000-0003-3816-7087)
- Daniel Inácio (ORCID: https://orcid.org/0000-0003-2541-208X)
- Liliana Oliveira (ORCID: https://orcid.org/0000-0001-5222-7600)
- Bruno Silva‐Santos (ORCID: https://orcid.org/0000-0003-4141-9302)
- Anita Quintal Gomes (ORCID: https://orcid.org/0000-0002-3348-0448)
- Ana Pamplona (ORCID: https://orcid.org/0000-0001-5338-2768)
- Carolina Cunha (ORCID: https://orcid.org/0000-0002-0639-4990)
- Daniel Sobral (ORCID: https://orcid.org/0000-0003-3955-0117)
- Alexandre M. Carmo (ORCID: https://orcid.org/0000-0002-2508-9799)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- University of Lisbon (PT)
- Inserm (FR)
- Universidade Politécnica de Lisboa (PT)
- National Institute of Health Dr. Ricardo Jorge (PT)
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto (PT)
- Instituto de Biologia Molecular e Celular
- Instituto Gulbenkian de Ciência (PT)
- Polytechnic Institute of Porto (PT)
Publication Details
- Journal
- Nature Immunology
- Published
- 2025-01-29
- DOI
- https://doi.org/10.1038/s41590-024-02073-8
- Citations
- 14
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 11.16
Funders
- Queen Mary University of London