# Circulating ex-Trm CD8 + T cells with skin-homing/chemoattraction phenotype are associated with disease severity in atopic dermatitis

**Authors:** Maria F. Ordóñez-Rubiano, Miguel Parra, Diana Bautista, Consuelo Romero-Sánchez

PMC · DOI: 10.3389/fmed.2026.1656289 · Frontiers in Medicine · 2026-02-09

## TL;DR

This study finds that a specific type of immune cell, CD8+ ex-Trm cells, is linked to more severe atopic dermatitis and may help track disease progression.

## Contribution

The study identifies CD8+ ex-Trm cells as a novel biomarker for disease severity in atopic dermatitis.

## Key findings

- CD8+ ex-Trm cells with skin-homing markers are increased in moderate-to-severe atopic dermatitis.
- These CD8+ cells correlate with clinical severity and may sustain inflammation by reseeding skin sites.
- CD4+ ex-Trm cells do not show similar expansion and may stay in inflamed skin.

## Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by skin-homing memory T cells. Recent evidence suggests that a subset of tissue-resident memory T (Trm) cells can exit tissues and recirculate as ex-Trm cells.

Peripheral blood memory T cell subpopulations were analyzed in adults with AD, stratified by disease severity, using multiparametric flow cytometry. CD4+ and CD8+ memory subsets and the skin-homing markers CLA, CCR4, and CCR10 were evaluated.

Overall CD4+ and CD8+ memory T cell distributions were preserved. AD patients showed expansion of CD4+ central memory T cells expressing CLA, CCR4, and CCR10. Most notably, a circulating population of CD8+ ex-Trm cells co-expressing CLA, CCR4, and CCR10 was increased in moderate-to-severe disease and correlated positively with clinical severity. No comparable expansion was observed for CD4+ ex-Trm cells.

Circulating CD8+ ex-Trm cells with skin-homing properties may contribute to AD progression by reseeding distant skin sites and sustaining inflammation, whereas CD4+ ex-Trm cells may remain preferentially retained within inflamed skin. These findings identify circulating CD8+ ex-Trm cells as potential biomarkers of disease severity and disease dissemination.

## Linked entities

- **Proteins:** SELPLG (selectin P ligand), CCR4 (C-C motif chemokine receptor 4), CCR10 (C-C motif chemokine receptor 10)
- **Diseases:** atopic dermatitis (MONDO:0004980)

## Full-text entities

- **Genes:** SELL (selectin L) [NCBI Gene 6402] {aka CD62L, LAM1, LECAM1, LEU8, LNHR, LSEL}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, SELE (selectin E) [NCBI Gene 6401] {aka CD62E, ELAM, ELAM1, ESEL, LECAM2, selectin-e}, CD27 (CD27 molecule) [NCBI Gene 939] {aka S152, S152. LPFS2, T14, TNFRSF7, Tp55}, CD69 (CD69 molecule) [NCBI Gene 969] {aka AIM, BL-AC/P26, CLEC2C, EA1, GP32/28, MLR-3}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CCR10 (C-C motif chemokine receptor 10) [NCBI Gene 2826] {aka GPR2}, CCR4 (C-C motif chemokine receptor 4) [NCBI Gene 1233] {aka CC-CKR-4, CD194, CKR4, CMKBR4, ChemR13, HGCN:14099}, SELPLG (selectin P ligand) [NCBI Gene 6404] {aka CD162, CLA, PSGL-1, PSGL1}, ITGA1 (integrin subunit alpha 1) [NCBI Gene 3672] {aka CD49a, VLA1}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, ITGAE (integrin subunit alpha E) [NCBI Gene 3682] {aka CD103, HUMINAE}
- **Diseases:** infectious disease (MESH:D003141), AD (MESH:D003876), systemic (MESH:D015619), allergies (MESH:D004342), cytotoxic (MESH:D064420), chronic pancreatitis (MESH:D050500), food allergies (MESH:D005512), infection (MESH:D007239), gastrointestinal infection (MESH:D005767), allergic rhinitis (MESH:D065631), Eczema (MESH:D004485), immunodeficiencies (MESH:D007153), viral infection (MESH:D014777), pruritus (MESH:D011537), autoinflammatory (MESH:D056660), allergic conjunctivitis (MESH:D003233), AS (MESH:D013167), autoimmune diseases (MESH:D001327), urticaria (MESH:D014581), asthma (MESH:D001249), graft-versus-host disease (MESH:D006086), cancer (MESH:D009369), sleep disturbance (MESH:D012893), skin disease (MESH:D012871), liver disease (MESH:D008107), inflammation (MESH:D007249), eosinophilic esophagitis (MESH:D057765), atopic (MESH:C566404)
- **Chemicals:** Tacrolimus (MESH:D016559), sodium (MESH:D012964), cyclosporine (MESH:D016572), CLA (MESH:C000626784), methotrexate (MESH:D008727), azathioprine (MESH:D001379)
- **Species:** Candida [taxon 1535326], Homo sapiens (human, species) [taxon 9606], Staphylococcus aureus (species) [taxon 1280], Malassezia (genus) [taxon 55193], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12926171/full.md

## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926171/full.md

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Source: https://tomesphere.com/paper/PMC12926171