García-Jiménez Irene, Sans-de San Nicolàs Lídia, Díez-Ribas Sandra, Curto-Barredo Laia, Bertolín-Colilla Marta, Vivancos-Melenchón Ana, Figueras-Nart Ignasi, Bonfill-Ortí Montserrat, Ryzhkova Anna, Ferran Marta, Czarnowicki Tali, Pujol Ramon M, Santamaria-Babí Luis F
Immunologia Translacional, Departament de Biologia Cellular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona (UB), Parc científic de Barcelona (PCB), Barcelona, Spain.
Programa de Doctorat en Biomedicina, Universitat de Barcelona (UB), Barcelona, Spain.
Front Immunol. 2025 Jul 1;16:1599892. doi: 10.3389/fimmu.2025.1599892. eCollection 2025.
Current understanding of IL-22 in atopic dermatitis (AD) mostly relies on animal models, intracellular staining of polyclonally activated peripheral lymphocytes, and biological therapies.
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 response.
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.
This is the first report showing that allergen-specific CLA T-cell-mediated IL-22 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.
目前对特应性皮炎（AD）中白细胞介素-22（IL-22）的认识主要依赖于动物模型、多克隆激活外周淋巴细胞的细胞内染色以及生物疗法。
我们使用循环记忆性皮肤淋巴细胞相关抗原（CLA）T细胞与自体皮损表皮细胞组成的共培养系统，评估了58例中重度AD患者对屋尘螨（HDM）提取物的IL-22反应。此外，我们对皮损皮肤活检进行了组织学和基因表达分析，评估了血浆中的特异性IgE水平，并将其与患者的临床特征一起与IL-22反应相关联。
HDM在记忆T细胞中引发异质性IL-22分泌，优先在CLA亚群中，这使得患者能够分为IL-22产生者（IL22P，n = 17）和非产生者（IL22NP，n = 41）。与IL22NP相比，IL22P表现出表皮厚度增加、皮损皮肤区域IL-22过表达、血浆中针对HDM和SEB的特异性IgE水平升高以及更高的促炎特征。
这是第一份报告，表明变应原特异性CLA T细胞介导的IL-22反应在功能上区分了具有特定临床特征且皮损皮肤中IL-22途径激活的中重度成年AD患者，为选择可能从IL-22导向治疗中获益的患者铺平了道路。
