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Review
. 2020 Jan;17(1):64-75.
doi: 10.1038/s41423-019-0291-4. Epub 2019 Oct 8.

Tissue-resident memory T cells and their biological characteristics in the recurrence of inflammatory skin disorders

Ling Chen  1 , Zhu Shen  2
Affiliations
Review

Tissue-resident memory T cells and their biological characteristics in the recurrence of inflammatory skin disorders

Ling Chen et al. Cell Mol Immunol. 2020 Jan.

Abstract

The skin is the largest organ of the body. The establishment of immunological memory in the skin is a crucial component of the adaptive immune response. Once naive T cells are activated by antigen-presenting cells, a small fraction of them differentiate into precursor memory T cells. These precursor cells ultimately develop into several subsets of memory T cells, including central memory T (TCM) cells, effector memory T (TEM) cells, and tissue resident memory T (TRM) cells. TRM cells have a unique transcriptional profile, and their most striking characteristics are their long-term survival (longevity) and low migration in peripheral tissues, including the skin. Under physiological conditions, TRM cells that reside in the skin can respond rapidly to pathogenic challenges. However, there is emerging evidence to support the vital role of TRM cells in the recurrence of chronic inflammatory skin disorders, including psoriasis, vitiligo, and fixed drug eruption, under pathological or uncontrolled conditions. Clarifying and characterizing the mechanisms that are involved in skin TRM cells will help provide promising strategies for reducing the frequency and magnitude of skin inflammation recurrence. Here, we discuss recent insights into the generation, homing, retention, and survival of TRM cells and share our perspectives on the biological characteristics of TRM cells in the recurrence of inflammatory skin disorders.

Keywords: Psoriasis; Recurrence; Skin inflammatory disorders; Tissue-resident Memory T cells.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Epidermal influx (① → ② → ③) of neutrophils from the peripheral blood in the early stage of psoriatic lesion initialization. Neutrophils form Munro’s microabscesses (③) when they reach the epidermis stratum corneum. The dotted line indicates the border between the epidermis and the dermis. Routine hematoxylin-eosin staining of psoriatic lesions at ×400 magnification are shown
Fig. 2
Fig. 2
Clinical images of the Koebner phenomenon. Psoriatic lesions develop in uninvolved (normal-appearing) skin at the site traumas. The accumulation and reactivation of memory T cells at these sites have been suggested to occur. Left, new linear psoriatic lesions occurred along scratches on the abdomen; Middle, new psoriatic lesions occurred on a scar from abdominal surgery; Right: psoriatic lesions occurred at the site of tattoo removal by medical laser on the leg. Asterisks, original psoriatic lesions; arrows, psoriatic lesions induced by trauma
Fig. 3
Fig. 3
CD103 on TRM cells is the main receptor for E-cadherin from epithelial cells or DCs. The interaction between CD103 and E-cadherin enhances cell–cell adhesion and the residence of TRM cells
Fig. 4
Fig. 4
The balance of PI3K/Akt signaling, the maintenance of JAK/STAT5 signaling, and their complex interplay in the survival of TRM cells. The activation of both PI3K/Akt signaling and JAK/STAT5 signaling support TRM cell survival (left). However, the constitutive activation of PI3K/Akt represses IL-7/IL-15 receptor expression and STAT5 phosphorylation (right)
Fig. 5
Fig. 5
The recurrence of cutaneous chronic inflammation frequently occurs in previously resolved sites. Therefore, immunological memory is proposed to be involved. Left, psoriatic lesions on the trunk recurred at previously resolved sites; Middle, recurrent fixed drug eruption on the buttock; Right, recurrent vitiligo lesions on the upper extremity. Arrow, recurrent lesions; asterisks, previously resolved areas
Fig. 6
Fig. 6
Immunofluorescence staining of sections from resolved psoriatic areas. (a) DAPI staining; (b) DAPI and CD8 staining; (c) DAPI and CD69 staining; (d) DAPI, CD8 and CD69 staining. The yellow in the merged image indicates CD8+CD69+ TRM cells in the resolved psoriatic areas (arrows)
See this image and copyright information in PMC

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