Heterogeneous IL-9 production by circulating skin-tropic and extracutaneous memory T cells in atopic dermatitis patients

García-Jiménez, Irene; Sans-de San Nicolás, Lídia; Curto Barredo, Laia; Bertolín Colilla, Marta; Sensada-López, Eloi; Figueras-Nart, Ignasi; Bonfill-Ortí, Montserrat; Guilabert, Antonio; Ryzhkova, Anna; Ferran Farrés, Marta; Damiani, Giovanni; Czarnowicki, Tali; Pujol Vallverdú, Ramon Maria; Santamaría-Babí, Luis Francisco

doi:http://dx.doi.org/10.3390/ijms25168569

Heterogeneous IL-9 production by circulating skin-tropic and extracutaneous memory T cells in atopic dermatitis patients

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García-Jiménez I, Sans-De San Nicolás L, Curto-Barredo L, Bertolín-Colilla M, Sensada-López E, Figueras-Nart I, Bonfill-Ortí M, Guilabert-Vidal A, Ryzhkova A, Ferran M, Damiani G, Czarnowicki T, Pujol RM, Santamaria-Babí LF. Heterogeneous IL-9 production by circulating skin-tropic and extracutaneous memory T cells in atopic dermatitis patients. Int J Mol Sci. 2024 Aug 6;25(16):8569. DOI: 10.3390/ijms25168569

Abstract

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.