House dust mite-derived IL-22 secretion by circulating CLA+ memory T cells identify atopic dermatitis patients with a distinct molecular signature in lesional skin

Summary: Abstract Body: IL-22-producing cells express the skin-homing markers CCR4, CCR6, CCR10 and the cutaneous lymphocyte-associated antigen (CLA), and are known to be the main source of this cytokine in atopic dermatitis (AD). Although the clinical relevance of IL-22 has been demonstrated by directed therapies, no studies have functionally explored the secretion of IL-22 by CLA+ memory T cells, in a physiological setting and in relationship with patients’ clinical features. To address this, we used a coculture of circulating memory CLA+/- T cells with autologous lesional epidermal cells activated with house dust mite (HDM) and quantified IL-22 levels in the supernatants. Production levels of IL-22 positively correlated with patients’ epidermal thickness of lesional areas as well as HDM- and staphylococcal enterotoxin B (SEB)-specific IgE plasma levels. IL-22 in vitro response by CLA+, but not CLA-, memory T cells enabled AD patient (n=60) stratification into IL-22 producers (IL22P) and non-producers (IL22NP). Lesional skin of IL22P showed increased epidermal hyperplasia, upregulation of IL22 mRNA expression and reduced expression of epidermal structural proteins (FLG, LOR). Because of a compromised skin barrier, they also exhibited increased IgE sensitization to HDM and SEB. Interestingly, the activation of cocultures with SEB elicited a distinct IL-22 response that was not associated with the clinical, histological and molecular features of the patients. Our results indicate that the IL-22 response induced by HDM allergen, but not SEB, identify a subgroup of patients that may benefit from anti-IL-22 targeted therapies. Irene García Jiménez¹, Lídia Sans de San Nicolàs¹, Laia Curto Barredo², Marta Bertolín Colilla², Ignasi Figueras Nart³, Anna Ryzhkova¹, Marta Ferran², Ramon M Pujol², Luis F Santamaria Babi¹ 1. Universitat de Barcelona, Barcelona, CT, Spain. 2. Hospital del Mar, Barcelona, CT, Spain. 3. Hospital de Bellvitge, Barcelona, Spain. Translational Studies: Preclinical