Author(s): Inácio, Daniel ; Amado, Tiago ; Pamplona, Ana ; Sobral, Daniel ; Cunha, Carolina ; Santos, Rita F. ; Oliveira, Liliana ; Rouquié, Nelly ; Carmo, Alexandre M. ; Lesourne, Renaud ; Gomes, Anita Q. ; Silva-Santos, Bruno
Date: 2025
Persistent ID: http://hdl.handle.net/10400.18/10613
Origin: Repositório Científico do Instituto Nacional de Saúde
Subject(s): γδ T cells; Transcriptome Analysis; Cytokines; Subset-Specific Regulators; Peripheral Activation; Genetics; Immunology
γδ T cells producing either interleukin-17A (γδ cells) or interferon-γ (γδ 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 cell versus γδ 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 cells versus γδ 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 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.
