The Jekyll and Hyde story of IL17-Producing γδT Cells.

In comparison to conventional alpha beta T cells, gamma delta T cells are considered as specialized T cells based on their contributions in regulating immune response. gamma delta T cells sense early environmental signals and initiate local immune-surveillance. The development of functional subtypes of gamma delta T 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 T gamma delta 1 requires strong TCR, CD27, and Skint-1 signals. However, differentiation of IL17-producing gamma delta T cells (T gamma delta 17) is independent of Skint-1 or CD27 but requires notch signaling along with IL6 and TGF beta cytokines in the presence of weak TCR signal. In response to cytokines like IL23, IL6, and IL1 beta, T gamma delta 17 outshine Th17 cells for early activation and IL17 secretion. Despite expressing similar repertoire of lineage transcriptional factors, cytokines, and chemokine receptors, T gamma delta 17 cells differ from Th17 in spatial and temporal fashion. There are compelling reasons to consider significant role of T gamma delta 17 cells in regulating inflammation and thereby disease outcome. T gamma delta 17 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 T gamma delta 17 cells inhibit Treg cells, exacerbate autoimmunity, and are also known to support carcinogenesis by enhancing angiogenesis. The mechanism associated with this dual behavior of T gamma delta 17 is not clear. To exploit, T gamma delta 17 cells for beneficial use requires comprehensive analysis of their biology. Here, we summarize the current understanding on the characteristics, development, and functions of T gamma delta 17 cells in various pathological scenarios.