ORIGINAL RESEARCH article

Front. Immunol.

Sec. Inflammation

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1599892

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

Provisionally accepted
Irene García-JiménezIrene García-Jiménez1,2Lídia Sans De San NicolàsLídia Sans De San Nicolàs1Sandra Díez-RibasSandra Díez-Ribas1Laia Curto-BarredoLaia Curto-Barredo3Marta Bertolín-ColillaMarta Bertolín-Colilla3Ana Vivancos-MelenchónAna Vivancos-Melenchón1Ignasi Figueras NartIgnasi Figueras Nart4Montserrat Bonfill-OrtíMontserrat Bonfill-Ortí4Anna RyzhkovaAnna Ryzhkova1Marta FerranMarta Ferran3Tali CzarnowickiTali Czarnowicki5Ramon M PujolRamon M Pujol3Luis F Santamaria-BabíLuis F Santamaria-Babí1*
  • 1Immunologia Translacional, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona (UB), Parc científic de Barcelona (PCB), Barcelona, Spain
  • 2Programa de doctorat en Biomedicina, Universitat de Barcelona (UB), Barcelona, Spain
  • 3Departament de Dermatologia, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
  • 4Departament de Dermatologia, Universitat de Barcelona (UB), L'Hospitalet de Llobregat, Spain
  • 5Dr. Phillip Frost Deparment of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, United States

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Background: Current understanding of IL-22 in atopic dermatitis (AD) mostly relies on animal models, intracellular staining of polyclonally activated peripheral lymphocytes, and biological therapies. Methods: We 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.Results: HDM 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. Conclusions: This 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.

Keywords: atopic dermatitis, CLA + memory T cells, Epidermal thickness, House dust mite, IgE, IL-22, Moderate-to-severe, stratification

Received: 25 Mar 2025; Accepted: 06 Jun 2025.

Copyright: © 2025 García-Jiménez, Sans De San Nicolàs, Díez-Ribas, Curto-Barredo, Bertolín-Colilla, Vivancos-Melenchón, Figueras Nart, Bonfill-Ortí, Ryzhkova, Ferran, Czarnowicki, Pujol and Santamaria-Babí. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Luis F Santamaria-Babí, Immunologia Translacional, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona (UB), Parc científic de Barcelona (PCB), Barcelona, Spain

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