Human αβ and γδ T Cells in Skin Immunity and Disease

Abstract

γδ T lymphocytes maintain skin homeostasis by balancing keratinocyte differentiation and proliferation with the destruction of infected or malignant cells. An imbalance in skin-resident T cell function can aggravate skin-related autoimmune diseases, impede tumor eradication, or disrupt proper wound healing. Much of the published work on human skin T cells attributes T cell function in the skin to αβ T cells, while γδ T cells are an often overlooked participant. This review details the roles played by both αβ and γδ T cells in healthy human skin and then focuses on their roles in skin diseases, such as psoriasis and alopecia areata. Understanding the contribution of skin-resident and skin-infiltrating T cell populations and cross-talk with other immune cells is leading to the development of novel therapeutics for patients. However, there is still much to be learned in order to effectively modulate T cell function and maintain healthy skin homeostasis.

Keywords: T cell; alopecia areata; diabetes; human; melanoma; psoriasis; skin immunity; γδ T cell.

Figure 1

Dendritic cells produce IL-12, IL-23, and TNF- α in response to pathogen-associated molecular pattern activation. These pro-inflammatory cytokines induce differentiation of naïve T cells into Th17 and Th22 cells. These T cells produce IL-22, IL-17A, and IL-17F causing epidermal hyperplasia and induce epidermal chemokine and inflammatory cytokine production. Neutrophils, T cells, mast cells, and NK cells are recruited to the skin and then to the epidermal/dermal junction via changes in adhesion molecule expression, such as VLA-1 (CD49a).

Figure 2

Expression of PD-1 and CTLA-4 by T cells leads to downregulation of activation and antitumor cytotoxic activity by suppressing downstream TCR signals. Immunotherapeutics have been approved that block CTLA-4 (ipilimumab) or programmed cell death protein 1 (PD1) (pembrolizumab, nivolumab) which restores the ability of T cells to become activated and destroy tumor cells.