Lesional dendritic cells in patients with chronic atopic dermatitis and psoriasis exhibit parallel ability to activate T-cell subsets.

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【作者】 Hideki Fujita  Avner Shemer  Mayte Suárez-Fari?as  Leanne M. Johnson-Huang  Suzanne J Tintle  Irma R Cardinale  Judilyn Fuentes-Duculan  Inna Novitskaya  John A. Carucci  James G. Krueger  E Guttman-Yassky 

【摘要】BACKGROUND Atopic dermatitis (AD) and psoriasis represent polar immune diseases. AD is a T(H)2/T(H)22-dominant disease, whereas psoriasis is considered a T(H)1/T(H)17 disease. Local immune deviation is suggested to be regulated by dendritic cell (DC)-induced T-cell polarization and recruitment of specific T-cell subsets by chemokines. Although the role of chemokines is well documented, the actual contribution of DCs to activate polar T-cell subsets in human subjects is still a matter of speculation. OBJECTIVE We sought to elucidate the significance of each cutaneous DC subset in disease-specific T-cell immune deviation. METHODS We performed a comprehensive analysis of major cutaneous resident (Langerhans cells and blood dendritic cell antigen 1-positive dermal DCs) and inflammatory (inflammatory dendritic epidermal cells and blood dendritic cell antigen 1-negative dermal DCs) DC subsets directly isolated from the lesional skin of patients with AD and those with psoriasis. RESULTS The ability of each DC subset to expand T(H)1, T(H)2, T(H)17, and T(H)22 subsets was similar between the 2 diseases, despite the association of both with accumulation of resident and inflammatory DCs. We also confirmed differential upregulation of chemokine expression in patients with AD (CCL17, CCL18, and CCL22) and psoriasis (CXCL1, IL-8, and CCL20). The expression of CCL17 and CCL22 was higher in Langerhans cells from patients with AD than from patients with psoriasis, whereas the opposite was observed for CXCL9 and CXCL10. CONCLUSION Our results suggest that DC polarity does not directly drive differential T-cell subset responses. Alternatively, disease-specific chemokines might recruit specific memory T-cell subsets into the skin, which in turn might be activated and expanded by DCs at the site of inflammation, maintaining differential immune polarity in these diseases.

【刊名】The Journal of allergy and clinical immunology