Allergen-specific circulating CLA+ memory T cells stratify IL-22 response in atopic dermatitis skin

BackgroundCurrent understanding of IL-22 in atopic dermatitis (AD) mostly relies on animal models, intracellular staining of polyclonally activated peripheral lymphocytes, and biological therapies.MethodsWe evaluated the IL-22 response to house dust mite (HDM) extract in 58 patients with moderate-to...

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Main Authors: Irene García-Jiménez, Lídia Sans-de San Nicolàs, Sandra Díez-Ribas, Laia Curto-Barredo, Marta Bertolín-Colilla, Ana Vivancos-Melenchón, Ignasi Figueras-Nart, Montserrat Bonfill-Ortí, Anna Ryzhkova, Marta Ferran, Tali Czarnowicki, Ramon M. Pujol, Luis F. Santamaria-Babí
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599892/full
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author Irene García-Jiménez
Irene García-Jiménez
Lídia Sans-de San Nicolàs
Sandra Díez-Ribas
Laia Curto-Barredo
Marta Bertolín-Colilla
Ana Vivancos-Melenchón
Ignasi Figueras-Nart
Montserrat Bonfill-Ortí
Anna Ryzhkova
Marta Ferran
Tali Czarnowicki
Ramon M. Pujol
Luis F. Santamaria-Babí
author_facet Irene García-Jiménez
Irene García-Jiménez
Lídia Sans-de San Nicolàs
Sandra Díez-Ribas
Laia Curto-Barredo
Marta Bertolín-Colilla
Ana Vivancos-Melenchón
Ignasi Figueras-Nart
Montserrat Bonfill-Ortí
Anna Ryzhkova
Marta Ferran
Tali Czarnowicki
Ramon M. Pujol
Luis F. Santamaria-Babí
author_sort Irene García-Jiménez
collection DOAJ
description BackgroundCurrent understanding of IL-22 in atopic dermatitis (AD) mostly relies on animal models, intracellular staining of polyclonally activated peripheral lymphocytes, and biological therapies.MethodsWe evaluated the IL-22 response to house dust mite (HDM) extract in 58 patients with moderate-to-severe AD using a coculture system made of circulating memory cutaneous lymphocyte associated antigen (CLA)+/− T cells with autologous lesional epidermal cells. Additionally, we performed histological and gene expression analysis in lesional skin biopsies, assessed specific IgE levels in plasma, and together with the clinical features of the patients, were related to the IL-22 in vitro response.ResultsHDM triggered heterogeneous IL-22 secretion in memory T cells, preferentially in the CLA+ subset, which enabled patient stratification into IL22 producers (IL22P, n=17) and non-producers (IL22NP, n=41). IL22P showed an increased degree of epidermal thickness, overexpression of IL22 in lesional skin areas, elevated specific IgE levels against HDM and SEB in plasma, and a higher proinflammatory profile compared to IL22NP.ConclusionsThis is the first report showing that allergen-specific CLA+ T-cell-mediated IL-22 in vitro response functionally distinguish moderate-to-severe adult AD patients with specific clinical features and activated IL-22 pathway in their lesional skin, paving the way for the selection of patients that may benefit from IL-22-directed therapies.
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spelling doaj-art-aa6bf2bb9b19463c8c64495f6eca5f072025-08-20T03:30:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15998921599892Allergen-specific circulating CLA+ memory T cells stratify IL-22 response in atopic dermatitis skinIrene García-Jiménez0Irene García-Jiménez1Lídia Sans-de San Nicolàs2Sandra Díez-Ribas3Laia Curto-Barredo4Marta Bertolín-Colilla5Ana Vivancos-Melenchón6Ignasi Figueras-Nart7Montserrat Bonfill-Ortí8Anna Ryzhkova9Marta Ferran10Tali Czarnowicki11Ramon M. Pujol12Luis F. Santamaria-Babí13Immunologia Translacional, Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona (UB), Parc científic de Barcelona (PCB), Barcelona, SpainPrograma de Doctorat en Biomedicina, Universitat de Barcelona (UB), Barcelona, SpainImmunologia Translacional, Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona (UB), Parc científic de Barcelona (PCB), Barcelona, SpainImmunologia Translacional, Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona (UB), Parc científic de Barcelona (PCB), Barcelona, SpainDepartament de Dermatologia, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), Barcelona, SpainDepartament de Dermatologia, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), Barcelona, SpainImmunologia Translacional, Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona (UB), Parc científic de Barcelona (PCB), Barcelona, SpainDepartament de Dermatologia, Universitat de Barcelona (UB), L’Hospitalet de, Llobregat, SpainDepartament de Dermatologia, Universitat de Barcelona (UB), L’Hospitalet de, Llobregat, SpainImmunologia Translacional, Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona (UB), Parc científic de Barcelona (PCB), Barcelona, SpainDepartament de Dermatologia, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), Barcelona, SpainDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartament de Dermatologia, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), Barcelona, SpainImmunologia Translacional, Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona (UB), Parc científic de Barcelona (PCB), Barcelona, SpainBackgroundCurrent understanding of IL-22 in atopic dermatitis (AD) mostly relies on animal models, intracellular staining of polyclonally activated peripheral lymphocytes, and biological therapies.MethodsWe evaluated the IL-22 response to house dust mite (HDM) extract in 58 patients with moderate-to-severe AD using a coculture system made of circulating memory cutaneous lymphocyte associated antigen (CLA)+/− T cells with autologous lesional epidermal cells. Additionally, we performed histological and gene expression analysis in lesional skin biopsies, assessed specific IgE levels in plasma, and together with the clinical features of the patients, were related to the IL-22 in vitro response.ResultsHDM triggered heterogeneous IL-22 secretion in memory T cells, preferentially in the CLA+ subset, which enabled patient stratification into IL22 producers (IL22P, n=17) and non-producers (IL22NP, n=41). IL22P showed an increased degree of epidermal thickness, overexpression of IL22 in lesional skin areas, elevated specific IgE levels against HDM and SEB in plasma, and a higher proinflammatory profile compared to IL22NP.ConclusionsThis is the first report showing that allergen-specific CLA+ T-cell-mediated IL-22 in vitro response functionally distinguish moderate-to-severe adult AD patients with specific clinical features and activated IL-22 pathway in their lesional skin, paving the way for the selection of patients that may benefit from IL-22-directed therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599892/fullatopic dermatitisCLA+ memory T cellsepidermal thicknesshouse dust miteIgEIL-22
spellingShingle Irene García-Jiménez
Irene García-Jiménez
Lídia Sans-de San Nicolàs
Sandra Díez-Ribas
Laia Curto-Barredo
Marta Bertolín-Colilla
Ana Vivancos-Melenchón
Ignasi Figueras-Nart
Montserrat Bonfill-Ortí
Anna Ryzhkova
Marta Ferran
Tali Czarnowicki
Ramon M. Pujol
Luis F. Santamaria-Babí
Allergen-specific circulating CLA+ memory T cells stratify IL-22 response in atopic dermatitis skin
Frontiers in Immunology
atopic dermatitis
CLA+ memory T cells
epidermal thickness
house dust mite
IgE
IL-22
title Allergen-specific circulating CLA+ memory T cells stratify IL-22 response in atopic dermatitis skin
title_full Allergen-specific circulating CLA+ memory T cells stratify IL-22 response in atopic dermatitis skin
title_fullStr Allergen-specific circulating CLA+ memory T cells stratify IL-22 response in atopic dermatitis skin
title_full_unstemmed Allergen-specific circulating CLA+ memory T cells stratify IL-22 response in atopic dermatitis skin
title_short Allergen-specific circulating CLA+ memory T cells stratify IL-22 response in atopic dermatitis skin
title_sort allergen specific circulating cla memory t cells stratify il 22 response in atopic dermatitis skin
topic atopic dermatitis
CLA+ memory T cells
epidermal thickness
house dust mite
IgE
IL-22
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599892/full
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