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Review
. 2017 Nov;152(3):372-381.
doi: 10.1111/imm.12791. Epub 2017 Aug 4.

Regulatory T cells in skin

Niwa Ali  1   2 , Michael D Rosenblum  1
Affiliations
Review

Regulatory T cells in skin

Niwa Ali et al. Immunology. 2017 Nov.

Abstract

Foxp3+ CD4+ regulatory T (Treg) cells are a subset of immune cells that function to regulate tissue inflammation. Skin is one of the largest organs and is home to a large proportion of the body's Treg cells. However, relative to other tissues (such as the spleen and gastrointestinal tract) the function of Treg cells in skin is less well defined. Here, we review our understanding of how Treg cells migrate to skin and the cellular and molecular pathways required for their maintenance in this tissue. In addition, we outline what is known about the specialized functions of Treg cells in skin. Namely, the orchestration of stem cell-mediated hair follicle regeneration, augmentation of wound healing, and promoting adaptive immune tolerance to skin commensal microbes. A comprehensive understanding of the biology of skin Treg cells may lead to novel therapeutic approaches that preferentially target these cells to treat cutaneous autoimmunity, skin cancers and disorders of skin regeneration.

Keywords: autoimmunity; regulatory T cells; skin.

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Figures

Figure 1
Figure 1
Skin regulatory T (Treg) cell trafficking and maintenance. (a) An abrupt wave of Treg cells accumulate in skin early in neonatal life. Commensal microbe elicitation of the chemokine CCL20 from hair follicle epithelial cells attracts CCR6‐expressing Treg cells to preferentially migrate to skin during this defined window of postnatal tissue development. (b) Treg cells in skin are maintained and/or induced by interactions with both epidermal Langerhans cells (LCs) and CD141+ dermal dendritic cells (DDCs). Skin‐homing Treg cells are defined by expression of CCR4, CD103, cutaneous lymphocyte antigen (CLA), and FuT7. ‘(M)’ or ‘(H)’ denotes pathways that have been identified in mouse or human, respectively.
Figure 2
Figure 2
Tissue specialized functions of regulatory T (Treg) cells in skin. (a) Subset of highly activated epidermal growth factor receptor (EGFR) ‐expressing Treg cells accumulate in skin early after full‐thickness wounding. These cells function to promote wound closure and re‐epithelialization through modulation of pro‐inflammatory macrophage induction. (b) A subpopulation of Treg cells in telogen skin localize in close proximity to hair follicle stem cells (HFSCs) in the bulge region of the hair follicle (HF). Treg cells facilitate hair regeneration through expression of the Notch ligand Jagged‐1 (Jag1), which is required to promote HF cycling by enhancing the activation and differentiation of HFSCs. ‘(M)’ or ‘(H)’ denotes pathways that have been identified in mouse or human, respectively.
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