Origin and Evolution of Dendritic Epidermal T Cells.

Area of Science:

• Immunology
• Developmental Biology
• Evolutionary Biology

Background:

• Dendritic epidermal T cells (DETCs) expressing invariant Vγ5Vδ1 T-cell receptors (TCRs) are crucial for mouse skin homeostasis, secreting cytokines that aid in immune responses and wound healing.
• The butyrophilin family gene, Skint1, specifically expressed in skin and thymus, has been identified as essential for DETC development in mice.
• Skint1 arose from a rodent-specific gene duplication, making Skint1-dependent DETCs unique to rodents.

Purpose of the Study:

• To investigate the evolutionary origins of dendritic epidermal T cells (DETCs) and their potential homologs across different vertebrate species.
• To understand the role of Skint1 in the development of unique rodent DETCs and compare this to the presence of similar cells in non-rodent species.

Main Methods:

• Comparative genomics to identify Skint1 orthologs in various species.
• Analysis of T-cell receptor (TCR) diversity in epidermal γδ T cells across mammals.
• Examination of γδ T-like lymphocytes in primitive vertebrates, such as lampreys, for DETC resemblance.

Main Results:

• Skint1 is a rodent-specific gene, indicating that Skint1-dependent DETCs are exclusive to rodents.
• Dendritic-shaped epidermal γδ T cells with limited antigen receptor diversity are present in other mammals.
• Lampreys, primitive vertebrates lacking TCRs, possess γδ T-like lymphocytes that resemble DETCs.

Conclusions:

• The need for innate-like T cells at the body surface is ancient, dating back to the origin of lymphocytes.
• DETC-like cells and their functions are conserved across a wide range of vertebrates, from mice to lampreys.
• While Skint1 is rodent-specific, the fundamental role of epidermal γδ T cells in innate immunity and tissue surveillance is evolutionarily ancient.