New insights on murine γδ T cells from single-cell multi-omics

Abstract

γδ T cells are a second T cell lineage conserved throughout evolution and across animal species that express a γδ T-cell receptor (TCR) consisting of a TCRγ and a TCRδ chain. γδ T cells develop in the murine thymus into various subsets with distinct functional potential that preferentially home to specific peripheral tissues, rather than lymphoid organs. The last decade has highlighted the biological importance of effector γδ T cell subsets producing either interferon (IFN)-γ (γδT1 cells) or interleukin (IL)-17 (γδT17 cells) in multiple (patho)physiological settings. These include key contributions of γδT1 and γδT17 cells to homeostasis and repair of the skin epithelium, and of γδT17cells to gingival mucosa homeostasis and repair, bone formation and fracture healing, regulation of adipose lipolysis, thermogenesis, and neurophysiology, by modulating neuronal synaptic plasticity. Additionally, γδ T cells also contribute to tissue physiology in infection and cancer settings. In infection, both γδT1 and γδT17 cells have been shown to play a non-redundant role in the host defense against skin infection (Staphylococcus aureus), and γδT17 cells have also been implied in the response to intestinal (Listeria monocytogenes) and lung (Clostridioides difficile) infections. On a more systemic level, γδT1 cells play a critical role in the control of viral load during cytomegalovirus (CMV) infection, and have been implicated in the immune response against malaria infection, with both benefic and pathogenic components described in different stages of Plasmodium infection.