Abstract
Gamma delta (GD) T cells are an unconventional T cell type present in both the epidermis and the dermis of human skin. They are critical to regulating skin inflammation, wound healing, and anti-microbial defense. Similar to CD8+ cytotoxic T cells expressing an alpha beta (AB) TCR, GD T cells have cytolytic capabilities. They play an important role in elimination of cutaneous tumors and virally infected cells and have also been implicated in pathogenicity of several autoimmune diseases. T cell cytotoxicity is associated with the expression of the pore forming protein Perforin. Perforin is an innate immune protein containing a membrane attack complex perforin-like (MACPF) domain and functions by forming pores in the membranes of target cells, which allow granzymes and reactive oxygen species to enter the cells and destroy them. Perforin-2, encoded by the gene MPEG1, is a newly discovered member of this protein family that is critical for clearance of intracellular bacteria. Cutaneous GD T cells express both Perforin and Perforin-2, but many questions remain regarding the role that these proteins play in GD T cell mediated cytotoxicity against tumors and bacterial pathogens. Here, we review what is known about Perforin expression by skin GD T cells and the mechanisms that contribute to Perforin activation.
Highlights
Gamma delta (GD) T cells are an unconventional T cell type that constitutes about 1–5% of circulating lymphocytes [1, 2]
We demonstrated that Perforin-2 expression is upregulated in CD45+ cells upon wounding in an ex vivo human skin model
Maintaining skin homeostasis and barrier function is essential for protection against physical and chemical stress, infections, and malignancies
Summary
Gamma delta (GD) T cells are an unconventional T cell type that constitutes about 1–5% of circulating lymphocytes [1, 2]. Perforin-2 is a recently identified member of the MACPF domain containing pore forming family of innate immune proteins that plays a critical role in clearance of intracellular bacterial infections. The mechanisms behind Perforin-2 activation and the extent of its contributions to host immunity have not been fully characterized.
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