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Review
. 2020 Dec 5;21(23):9286.
doi: 10.3390/ijms21239286.

Skin Resident γδ T Cell Function and Regulation in Wound Repair

Luis D Munoz  1 , Michael J Sweeney  1 , Julie M Jameson  1
Affiliations
Review

Skin Resident γδ T Cell Function and Regulation in Wound Repair

Luis D Munoz et al. Int J Mol Sci. .

Abstract

The skin is a critical barrier that protects against damage and infection. Within the epidermis and dermis reside γδ T cells that play a variety of key roles in wound healing and tissue homeostasis. Skin-resident γδ T cells require T cell receptor (TCR) ligation, costimulation, and cytokine reception to mediate keratinocyte activity and inflammatory responses at the wound site for proper wound repair. While both epidermal and dermal γδ T cells regulate inflammatory responses in wound healing, the timing and factors produced are distinct. In the absence of growth factors, cytokines, and chemokines produced by γδ T cells, wound repair is negatively impacted. This disruption in γδ T cell function is apparent in metabolic diseases such as obesity and type 2 diabetes. This review provides the current state of knowledge on skin γδ T cell activation, regulation, and function in skin homeostasis and repair in mice and humans. As we uncover more about the complex roles played by γδ T cells in wound healing, novel targets can be discovered for future clinical therapies.

Keywords: DETC; T cell; chemokine; cytokine; dermis; diabetes; epidermis; obesity; wound repair; γδ T cell.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Typical cellular crosstalk occurring in murine wound repair. During wound repair, interleukin-15 (IL-15) is secreted by keratinocytes to activate epidermal γδ T cells to release insulin-like growth factor-1 (IGF-1) and prevent keratinocyte apoptosis. Chemokine ligand 20 (CCL20) is released by keratinocytes to recruit dermal γδ T cells expressing IL-17A and induce local inflammation. IL-17A is also released by epidermal γδ T cells to activate proliferation, differentiation, and migration of keratinocytes.
Figure 2
Figure 2
Obesity and type 2 diabetes cause alterations in cellular crosstalk that result in delayed wound repair. Epidermal γδ T cells become reduced in number, causing premature keratinocyte differentiation, epidermal thinning, and reduced production of interleukin-15 (IL-15) and IL-17. Upon wounding, the decreased number and function of γδ T cells result in a reduction in insulin-like growth factor-1 (IGF-1) and decreased keratinocyte proliferation. In addition, less chemokine ligand 20 (CCL20) is produced by keratinocytes, hindering the recruitment of dermal γδ T cells to the epidermis. Together, this leads to a delay in wound repair.
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