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Review
. 2020 Jul 29:11:1656.
doi: 10.3389/fimmu.2020.01656. eCollection 2020.

Get in Touch With Dendritic Epithelial T Cells!

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Review

Get in Touch With Dendritic Epithelial T Cells!

Flavian Thelen et al. Front Immunol. .

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.

Keywords: DETC; activation; costimulation; epidermis; epithelial; γδT cell.

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Figures

Figure 1
Figure 1
Epithelial architecture and immune cell distribution. The epidermis is divided from the dermis by the basal membrane. The epidermis is composed of four distinct layers: the stratum corneum, stratum granulosum, stratum spinosum and basal layer. These layers are composed mainly of KC that are infiltrated with immune cells, such as DETC, LC, and CD8+ TRM. DETC precursors in neonatal mice, home to the epidermis via the blood vessels and following the chemotactic gradient of KC-derived CCL27. DETC and LC form stable interactions with KC tight junctions, whereas CD8+ TRM migrate along the basal layer and in-between KC. DETC produce multiple soluble factors that promote KC survival and proliferation and receive IL-15 from KC, which promotes their lifelong survival and self-renewal.
Figure 2
Figure 2
Direct cell-cell contacts regulating immune surveillance of epidermis. DETC and KC form stable interactions during steady state (bottom). TCR and adhesion molecules LFA-1 and CD103 are enriched and engaged with KC-derived ligands at tips of DETC protrusions. LC-KC interaction via CD200R-CD200 suppresses LC activation at steady state. Stressed KC (top) upregulates costimulatory ligands and DETC-specific antigens, which activate DETC via JAML, CD100, NKG2D, and TCR. However, further research is needed to pinpoint the role of antigen presentation and CD200-CD200R signaling in shaping DETC effector functions (indicated by “?”).

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