T cells in chronic spontaneous urticaria show skin-migratory capacity and endotype-specific differences

Chronic spontaneous urticaria (CSU) is characterized by recurrent itchy wheals. As CD4⁺ T cells are observed in lesional infiltrates and treatments compromising T-cellular functions are effective, they might play an important role in the pathogenesis of CSU. However, their exact impact remains unclear.

T cell subsets in CSU patients (n = 59) and healthy controls (HC; n = 18) were characterized by expression of surface markers and secretion of cytokines (IL-17, IL-5, IFNγ, IL-10, IL-31) utilizing flow cytometry and ELISpot analysis. The skin-migratory capacity of T cell subsets was assessed by analyzing the expression of skin-homing markers (CLA, CCR10, CCR8) by flow cytometry. CSU endotypes of patients were classified into autoallergic and autoimmune by measuring serum levels of anti-TPO-antibodies and anti-IL-24-IgE by ELISA, and serum autoreactivity by basophil activation test.

Circulating Th, follicular Th, and regulatory T cells were equally distributed among CSU patients and HC. However, CD4⁺ T cells of CSU patients showed significantly higher expression of CLA, with an increased frequency of Th2 and Th17 cells among CLA⁺CD4⁺ memory T cells. While Th2 cells prevailed in autoallergic CSU, Th17 and Th1 cells predominated in autoimmune CSU. Moreover, significantly fewer IL-17-, IFNγ-, and IL-10-secreting T cells were observed in peripheral blood of CSU patients.

Peripheral blood T cells of CSU patients exhibit an enhanced skin-migratory capacity, with Th2 and Th17/Th1 subsets differentially involved according to the endotype of either autoallergic or autoimmune CSU. These findings could indicate potential targets for novel therapeutic applications.