Innately versatile: γδ17 T cells in inflammatory and autoimmune diseases

Abstract

IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation. However, given their transcriptional and epigenetic wiring, γδ17 T cells are permissive to different environmental instructions, and can readily acquire the ability to co-produce multiple cytokines, such as IFN-γ, IL-22 and GM-CSF, that further propagate inflammation. Moreover, strong IL-23 signals, which are abundantly found in autoinflammatory conditions, are able to induce de novo differentiation of γδ17 T cells from uncommitted precursors, both in mice and humans. This notwithstanding, the exact mechanisms responsible for γδ17 T cell pathogenicity and multifunctionality are still poorly understood, especially in humans. The pathogenic roles attributed to γδ17 T cells in autoimmune diseases stem mainly from their ability to recruit different inflammatory myeloid populations to the target tissue, and to modulate αβ T cell function, either by enhancing inflammatory T17 responses, or by restraining regulatory T cell activity. Given their capacity to link key inflammatory axes of innate and adaptive immunity, a better understanding of the molecular basis underpinning γδ17 T cell plasticity, and how much this feature accounts for their pathophysiological roles, may be critical for developing novel therapeutic approaches. In this review, we discuss the importance of γδ17 T cells in breaking tolerance and enhancing inflammation in various autoimmune diseases, such as multiple sclerosis, psoriasis and rheumatoid arthritis under the light of their basic biological traits, e.g. development, activation, effector functions and plasticity.

Extracellular vesicles derived from injured vascular tissue promote the formation of tertiary lymphoid structures in vascular allografts

“…Indeed, γδKO allograft recipients formed fewer autoantibodies upon ApoExo injection and showed lower expression of IL‐17 within vascular allografts and reduced TLS formation. These observations are in line with previous studies showing that human IL‐17‐producing γδT cells are generated in the periphery and can be recruited to inflamed tissues where they accumulate . This process takes place more rapidly compared to the activation of conventional T lymphocytes as γδT cells can be activated in the absence of a cognate TCR ligand .…”

“…33 γδT cells are generated in the periphery and can be recruited to inflamed tissues where they accumulate. 36,37 This process takes place more rapidly compared to the activation of conventional T lymphocytes 38 as γδT cells can be activated in the absence of a cognate TCR ligand. 38 The mechanism by which ApoExo activate γδT cells is still ill defined, but our results identify the proteasome activity of ApoExo as a pivotal signal regulating trafficking of γδT cells to sites of vascular injury.…”

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

“…Inflammatory Bowel Disease (IBD), psoriasis and asthma etc.) and neurodegeneration along with tissue homeostasis and repair [194][195][196][197][198][199]. γδT cells constitute minor (2%-10% of CD3 + T cells) but a very important component of the T-cell population in peripheral circulation in humans.…”

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

“…Identication of differentially abundant immune cell subsets offers a glimpse into potential immune mechanisms contributing to PBC. Gamma-delta T cells are non-conventional T cells with a restricted T cell receptor repertoire often conceived as forming a bridge between innate and adaptive immunity 20 . In our study, the peripheral gamma-delta T cell population was found to be reduced in PBC compared to controls, visually on the FlowSOM-MST map and quantitatively in FlowSOM metacluster and cluster analyses.…”