Diversity of Skin-resident γδ T Cells

γδ T cell population in the skin is a fascinating subject of study because of its remarkable diversity and multifaceted functions. In this article, Creative Biolabs takes a journey into the complex world of skin-resident γδ T cells and discovers their multifunctionality in terms of phenotype, function, and interactions with other immune cells.

Understanding Skin-resident γδ T Cells

γδ T cells are known for their versatility, with subsets of these cells carefully tuned to perform specific functions in immune surveillance, tissue repair, and local immune response modulation. In the skin, these cells are on the front lines, ready to respond to challenges ranging from pathogens to cellular stress.

The Vγ9Vδ2 T cell population is one of the most intensively studied subpopulations of cutaneous γδ T cells. These cells are of great interest for their ability to recognize and respond to phosphoantigens, intermediates in the mevalonate pathway produced by bacteria and some stressed host cells.

Phenotypic Diversity

One of the most striking aspects of skin-resident γδ T cells is their remarkable diversity. Researchers have uncovered a plethora of distinct subsets within the skin's γδ T cell population, each with its own functional specialization. These subsets include but are not limited to:

• Epidermal γδ T cells: These cells predominantly reside in the epidermis and are characterized by the expression of markers such as CD103 and CD49a. They play a critical role in wound healing and epithelial tissue repair.
• Dermal γδ T cells: Found in the dermal layer of the skin, these cells often express CD27 and CD45RB. They are involved in immunoregulation and contribute to the control of inflammation.
• IL-17 Producing γδ T Cells: Some skin-resident γδ T cells specialize in producing the cytokine IL-17, contributing to the regulation of local immune responses, particularly in the context of autoimmune diseases and inflammatory skin conditions.
• Tissue-Resident Memory T Cells (TRM): TRM cells are a subset of γδ T cells that reside long-term within peripheral tissues, such as the skin. They are strategically positioned to provide rapid and targeted immune responses upon reinfection, forming a critical component of immunological memory.

Functional Diversity

Skin-resident γδ T cells are versatile in their functions, further underscoring their importance in skin health.

Fig. 1 Model of functions of skin-resident γδ T Cells.¹

• Antimicrobial Defense: Many γδ T cell subsets possess potent antimicrobial capabilities, enabling them to directly eliminate infected cells and produce antimicrobial molecules like defensins and granzymes.
• Wound Healing: Epidermal γδ T cells are actively involved in wound healing by promoting keratinocyte proliferation and tissue repair.
• Immunoregulation: Certain subsets, like dermal γδ T cells, help maintain immune homeostasis in the skin by regulating the activity of other immune cells, such as dendritic cells and T cells.
• Tumor Surveillance: Emerging research suggests that γδ T cells, including skin-resident subsets, may play a role in monitoring and responding to skin cancers.

Interaction with Other Immune Cells

Skin-resident γδ T cells do not work in isolation; they engage in intricate crosstalk with other immune cells, orchestrating a harmonious defense system within the skin.

• γδ T cells interact with dendritic cells to facilitate the presentation of antigens to αβ T cells, influencing adaptive immune responses.
• They collaborate with resident macrophages to clear cellular debris and apoptotic cells, thereby maintaining a clean and infection-free skin environment.

The rich diversity of skin-resident γδ T cells offers exciting avenues for therapeutic exploration. Researchers are actively investigating how to utilize the unique properties of these cells for medical applications, including immunotherapy and vaccine development. Creative Biolabs is at the forefront of this scientific quest, and we are exploring the unique functions and regulatory mechanisms of various γδ T cell subsets.

Reference

1. MacLeod, Amanda S., and Wendy L. Havran. "Functions of skin-resident γδ T cells." Cellular and molecular life sciences 68 (2011): 2399-2408.