Get in Touch With Dendritic Epithelial T Cells!

Abstract

Innate and adaptive immune systems continuously interchange information and orchestrate their immune responses to protect the host. γδT cells play crucial roles, as they incorporate both innate and adaptive immune characteristics. Dendritic epidermal T cells (DETC) are specialized γδT cells, which are uniquely positioned to rapidly respond to skin wounds and infections. Their elongated dendrite morphology allows them to be in continuous contact with multiple neighboring keratinocytes and Langerhans cells. Cellular interactions are fundamental to the formation, activation and maintenance of immune cell functions during steady state and pathology. Recent technological advances, especially in the field of cellular imaging, have contributed greatly to the characterization of complex cellular interactions in a spatiotemporally resolved manner. In this review, we will highlight the often-underappreciated function of DETC and other γδT cells during steady state and an ongoing immune response. More specifically, we discuss how DETC-precursors are shaped in the fetal thymus during embryogenesis as well as how direct cell-cell interactions of DETC with neighboring epidermal cells shape skin homeostasis and effector functions. Furthermore, we will discuss seminal work and recent discoveries made in the γδT cell field, which have highlighted the importance of γδT cells in the skin, both in humans and mice.

H19 promotes aerobic glycolysis, proliferation, and immune escape of gastric cancer cells through the microRNA‐519d‐3p/lactate dehydrogenase A axis

“…Therefore, we asked whether H19 was able to modulate tumor immune response through the miR‐519d‐3p/LDHA/lactate axis. As shown in Figure 7A, CM from stable knockdown H19 GC cells clearly elevated the population of IFN‐γ‐positive (IFN‐γ + ) γδT cells, an important antitumor immune cell 32 . Moreover, treatment with lactate counteracted the increases in the population of IFN‐γ + γδT cells induced by CM from stable knockdown H19 GC cells (Figure 7A).…”

Regulatory T cells promote innate inflammation after skin barrier breach via TGF-β activation

“…2A). This region forms the functional skin barrier and is preferentially inhabited by dendritic epidermal T cells (DETCs) expressing a restricted γδ T cell receptor (TCRγδ) ( 26 ). To further elucidate skin T reg epithelial interactions, we used an established enzymatic approach to separate skin epithelium from dermal layers ( 27 ).…”

T-Cell Adhesion in Healthy and Inflamed Skin

“…Effector and memory CD4 + T cells are also commonly observed around hair follicles; however, these cells also patrol within the dermis (Collins et al 2016;Gaylo et al 2016;Gebhardt et al 2011). In contrast, CD8 + T cells and DETCs preferentially associate with the epidermal basement membrane, although in healthy human skin a relatively large proportion of CD8s inhabit the epidermis and are capable of migrating back and forth between the dermis and epidermis (Cheuk et al 2014;Dijkgraaf et al 2019;Gebhardt et al 2011;Thelen and Witherden 2020).…”

“…Effector and memory CD4 + T cells are also commonly observed around the HFs; however, these cells also patrol within the dermis ( Collins et al., 2016 ; Gaylo et al., 2016 ; Gebhardt et al., 2011 ). In contrast, CD8 + T cells and DETCs preferentially associate with the epidermal basement membrane (BM), although in healthy human skin, a relatively large proportion of CD8s inhabit the epidermis and are capable of migrating back and forth between the dermis and epidermis ( Cheuk et al., 2014 ; Dijkgraaf et al., 2019 ; Gebhardt et al., 2011 ; Thelen and Witherden, 2020 ). Interstitial motility of skin T cells was presumed to be through integrin-independent amoeboid crawling, as has been described in lymph nodes and for myeloid cells ( Gaylo et al., 2016 ; Jacobelli et al., 2009 ; Lämmermann et al., 2008 ; Weninger et al., 2014 ).…”