Mixing Signals: Molecular Turn Ons and Turn Offs for Innate γδ T-Cells

Abstract

Lymphocytes of the gamma delta (γδ) T-cell lineage are evolutionary conserved and although they express rearranged antigen-specific receptors, a large proportion respond as innate effectors. γδ T-cells are poised to combat infection by responding rapidly to cytokine stimuli similar to innate lymphoid cells. This potential to initiate strong inflammatory responses necessitates that inhibitory signals are balanced with activation signals. Here, we discuss some of the key mechanisms that regulate the development, activation, and inhibition of innate γδ T-cells in light of recent evidence that the inhibitory immunoglobulin-superfamily member B and T lymphocyte attenuator restricts their differentiation and effector function.

Editorial: “Recent advances in gamma/delta T cell biology: new ligands, new functions, and new translational perspectives”

“…The signaling pathways governing γδ T cell differentiation and activation have been discussed in contributions from Carl Wares’s ( 1 ) and Bruno Silva-Santos’s ( 2 ) groups. Ribeiro et al discuss the control of γδ T cell activation and differentiation by distinct classes of cell surface receptors, namely (i) the TCR, (ii) costimulatory receptors (with a focus on CD27), (iii) cytokine receptors, (iv) NK receptors, and (v) inhibitory receptors.…”

“…Bekiaris et al focus on the cytokine control of innate γδ T cells, and discuss the role of IL-7 in being critical for thymic development of γδ T cells by regulating the survival of progenitor cells and inducing V(D)J recombination within the TCRγ gene locus. IL-7 also supports homeostatic proliferation of γδ T cells and regulates surface expression of BTLA in a STAT5-dependent manner ( 1 ).…”

Mapping of γ/δ T cells Reveals Vδ2 T cells Resistance to Senescence

“…γδ T cells are classified in between the adaptive and the innate immune system as they exhibit faster immune response to new infections compared to αβ T cells [6]. While αβ T cells react to major histocompatibility complex (MHC)-Class bound peptides, γδ T cells recognize a range of molecules and are not entirely MHC-Class dependent [7,8]. For instance, Vδ1+ react against stress-induced molecules such as MICA, MICB and ULBPs on infected or transformed cells [9,10].…”

Benzoxazepines Achieve Potent Suppression of IL‐17 Release in Human T‐Helper 17 (TH17) Cells through an Induced‐Fit Binding Mode to the Nuclear Receptor RORγ

“…The nuclear hormone receptor RORγt, an isoform of the retinoic acid‐related orphan receptor gamma (RORc, RORγ), is exclusively expressed in cells of the immune system and was shown to be the master regulator for function and development of T H 17 cells and related IL‐17‐producing cells such as innate lymphoid 3 cells and γ δ T cells . The potential to modulate RORγt with orally bioavailable small molecules rather than suppressing a single cytokine, has generated a strong interest in this target for the treatment of inflammatory disorders …”