Heterogeneous IL-9 Production by Circulating Skin-Tropic and Extracutaneous Memory T Cells in Atopic Dermatitis Patients

• Published in: International journal of molecular sciences 2024-08, Vol.25 (16), p.8569
• Main Authors: García-Jiménez, Irene, Sans-de San Nicolás, Lídia, Curto-Barredo, Laia, Bertolín-Colilla, Marta, Sensada-López, Eloi, Figueras-Nart, Ignasi, Bonfill-Ortí, Montserrat, Guilabert-Vidal, Antonio, Ryzhkova, Anna, Ferran, Marta, Damiani, Giovanni, Czarnowicki, Tali, Pujol, Ramon M, Santamaria-Babí, Luis F
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Allergens; Allergens - immunology; Allergies; Animals; Antigens, Differentiation, T-Lymphocyte - metabolism; atopic dermatitis; cutaneous lymphocyte-associated antigen; Cytokines; Dermatitis; Dermatitis, Atopic - immunology; Dermatitis, Atopic - metabolism; Disease; Enterotoxins - immunology; extracutaneous; Female; heterogenous; house dust mite; Humans; Immunoglobulin E - blood; Immunoglobulin E - immunology; interleukin-9; Interleukin-9 - metabolism; Lymphocytes; Male; Membrane Glycoproteins; Memory T Cells - immunology; Memory T Cells - metabolism; Middle Aged; Pyroglyphidae - immunology; Signal transduction; Skin - immunology; Skin - metabolism; Young Adult
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25168569

Interleukin (IL)-9 is present in atopic dermatitis (AD) lesions and is considered to be mainly produced by skin-homing T cells expressing the cutaneous lymphocyte-associated antigen (CLA). However, its induction by AD-associated triggers remains unexplored. Circulating skin-tropic CLA and extracutaneous/systemic CLA memory T cells cocultured with autologous lesional epidermal cells from AD patients were activated with house dust mite (HDM) and staphylococcal enterotoxin B (SEB). Levels of AD-related mediators in response to both stimuli were measured in supernatants, and the cytokine response was associated with different clinical characteristics. Both HDM and SEB triggered heterogeneous IL-9 production by CLA and CLA T cells in a clinically homogenous group of AD patients, which enabled patient stratification into IL-9 producers and non-producers, with the former group exhibiting heightened HDM-specific and total IgE levels. Upon allergen exposure, IL-9 production depended on the contribution of epidermal cells and class II-mediated presentation; it was the greatest cytokine produced and correlated with HDM-specific IgE levels, whereas SEB mildly induced its release. This study demonstrates that both skin-tropic and extracutaneous memory T cells produce IL-9 and suggests that the degree of allergen sensitization reflects the varied IL-9 responses in vitro, which may allow for patient stratification in a clinically homogenous population.