The Jekyll and Hyde story of IL17-Producing γδT Cells

Abstract

In comparison to conventional αβT cells, γδT cells are considered as specialized T cells based on their contributions in regulating immune response. γδT cells sense early environmental signals and initiate local immune-surveillance. The development of functional subtypes of γδT cells takes place in the thymus but they also exhibit plasticity in response to the activating signals and cytokines encountered in the extrathymic region. Thymic development of Tγδ1 requires strong TCR, CD27, and Skint-1 signals. However, differentiation of IL17-producing γδT cells (Tγδ17) is independent of Skint-1 or CD27 but requires notch signaling along with IL6 and TGFβ cytokines in the presence of weak TCR signal. In response to cytokines like IL23, IL6, and IL1β, Tγδ17 outshine Th17 cells for early activation and IL17 secretion. Despite expressing similar repertoire of lineage transcriptional factors, cytokines, and chemokine receptors, Tγδ17 cells differ from Th17 in spatial and temporal fashion. There are compelling reasons to consider significant role of Tγδ17 cells in regulating inflammation and thereby disease outcome. Tγδ17 cells regulate mobilization of innate immune cells and induce keratinocytes to secrete anti-microbial peptides thus exhibiting protective functions in anti-microbial immunity. In contrast, dysregulated Tγδ17 cells inhibit Treg cells, exacerbate autoimmunity, and are also known to support carcinogenesis by enhancing angiogenesis. The mechanism associated with this dual behavior of Tγδ17 is not clear. To exploit, Tγδ17 cells for beneficial use requires comprehensive analysis of their biology. Here, we summarize the current understanding on the characteristics, development, and functions of Tγδ17 cells in various pathological scenarios.

Early production of IL‐17A by γδ T cells in the trachea promotes viral clearance during influenza infection in mice

“…4D). We also measured in tracheal lavage the levels of the cytokines IL‐23, IL‐1β, and IL‐6 that are known to promote the expression of IL‐17A in γδ T cells . We observed a significant upregulation of all cytokines in comparison to uninfected controls (Fig.…”

Exposure to Plasmodium vivax is associated with the increased expression of exhaustion markers on γδ T lymphocytes

“…Several studies have established the importance of γδ T cells in efficiently combating infectious diseases; however, these cells can also aggravate inflammatory diseases . The frequency of γδ T cells is known to be increased in the peripheral blood of acute Plasmodium infected patients .…”

A Retrospective Analysis of γδ T Cell Expression in Chronic Rhinosinusitis and Its Association with Recurrence of Nasal Polyps

“…An increased expression of γδ T cells was detected in the lung of asthmatic patients, which exacerbated Th1/Th2 disturbance and inflammation [45]. γδ T cells, like innate cells, are also involved in early immune responses, producing proinflammatory cytokines (INF-γ, IL-17, TNF-α), and activate adaptive immune cells [46]. The expression of IL-17 has been reported to be increased in the nasal mucosa of CRSwNP patients and is closely related to the infiltration of eosinophils and neutrophils [47,48,49].…”