Pathogenic CD8+ epidermis-resident memory T cells displace dendritic epidermal T cells in allergic dermatitis

TY - JOUR

T1 - Pathogenic CD8+ epidermis-resident memory T cells displace dendritic epidermal T cells in allergic dermatitis

AU - Ø Gadsbøll, Anne-Sofie

AU - Jee, Mia H

AU - Funch, Anders B

AU - Alhede, Maria

AU - Mraz, Veronika

AU - Weber, Julie F

AU - Callender, Lauren A

AU - Carroll, Elizabeth C

AU - Bjarnsholt, Thomas

AU - Woetmann, Anders

AU - Ødum, Niels

AU - Thomsen, Allan R

AU - Johansen, Jeanne D

AU - Henson, Sian M

AU - Geisler, Carsten

AU - Bonefeld, Charlotte M

N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2020/4

Y1 - 2020/4

N2 - The skin is our interface with the outside world, and consequently it is exposed to a wide range of microbes and allergens. Recent studies have indicated that allergen-specific skin-resident memory T (TRM) cells play a role in allergic contact dermatitis (ACD). However, the composition and dynamics of the epidermal T-cell subsets during ACD are not known. Here we show that exposure of the skin to the experimental contact allergen DNFB results in a displacement of the normally occurring dendritic epidermal T cells (DETC) concomitant with an accumulation of epidermal CD8+CD69+CD103+ TRM cells in mice. By studying knockout mice, we provide evidence that CD8+ T cells are required for the displacement of the DETC and that DETC are not required for recruitment of CD8+ TRM cells to the epidermis following allergen exposure. We demonstrate that the magnitude of the allergic reaction correlates with the number of CD8+ epidermal TRM cells, which again correlates with allergen dose and number of allergen exposures. Finally, in an attempt to elucidate why CD8+ epidermal TRM cells persist in the epidermis, we show that CD8+ epidermal TRM cells have a higher proliferative capability and are bioenergetically more stable, displaying a higher spare respiratory capacity than DETC.

AB - The skin is our interface with the outside world, and consequently it is exposed to a wide range of microbes and allergens. Recent studies have indicated that allergen-specific skin-resident memory T (TRM) cells play a role in allergic contact dermatitis (ACD). However, the composition and dynamics of the epidermal T-cell subsets during ACD are not known. Here we show that exposure of the skin to the experimental contact allergen DNFB results in a displacement of the normally occurring dendritic epidermal T cells (DETC) concomitant with an accumulation of epidermal CD8+CD69+CD103+ TRM cells in mice. By studying knockout mice, we provide evidence that CD8+ T cells are required for the displacement of the DETC and that DETC are not required for recruitment of CD8+ TRM cells to the epidermis following allergen exposure. We demonstrate that the magnitude of the allergic reaction correlates with the number of CD8+ epidermal TRM cells, which again correlates with allergen dose and number of allergen exposures. Finally, in an attempt to elucidate why CD8+ epidermal TRM cells persist in the epidermis, we show that CD8+ epidermal TRM cells have a higher proliferative capability and are bioenergetically more stable, displaying a higher spare respiratory capacity than DETC.

U2 - 10.1016/j.jid.2019.07.722

DO - 10.1016/j.jid.2019.07.722

M3 - Journal article

C2 - 31518559

SN - 0022-202X

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

ER -