γδ and αβ T cells develop in the thymus from common progenitor cells. 1 Unlike αβ T cells, the majority of murine γδ T cells are functionally committed during intra-thymic differentiation. 2-4 This underlines the importance of the thymic microenvironment in the regulation of the peripheral effector functions of γδ T cells. Central to the thymic microenvironment is the thymic epithelial cells (TEC), divided into cortical TEC (cTEC) and medullary TEC (mTEC). 5 Particularly, the mTEC seem to regulate the functional commitment of γδ T cells within the thymus. Recently, it has become clear that TEC, especially mTEC, are more heterogeneous than previously assumed. Interestingly, subsets of mTEC with expression profiles such as tuft cells and keratinocytes (KC) have been identified. 6,7 KC constitute the majority of cells within the outermost layer of the skin, the epidermis. The epidermis acts as our first line of defense against assaults from pathogens, chemicals, and allergens, thereby playing a critical role in providing protection from injury. Although KC are not classified as immune cells, they play important immunological roles in the first line of defense against pathogens and allergens. Thus, KC express pattern recognition receptors such as Toll-like receptors (TLR) 8 and NOD-like receptors (NLR), 9 some constitutively and others following stimulation, that are able to recognize pathogen-associated molecular patterns and damage-associated molecular patterns, which trigger the production and release of cytokines, chemokines, and anti-microbial peptides that in turn activate immune cells in the skin. 10-12 The immune cells found in the epidermis are T cells and a subset of antigen-presenting cells termed Langerhans cells (LC). 10,12,13 In naïve mice, the primary subset of T cells in the epidermis is a special subset of γδ T cells called dendritic epidermal T cells (DETC) due to their dendritic morphology. 14