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题目:: Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype.
作者:: Gaudenzio(Nicolas),Laurent(Camille),Valitutti(Salvatore),Espinosa(Eric)
状态:: 发布时间2013-04-29 , 更新时间 2014-01-14
期刊:: J Allergy Clin Immunol
摘要:: Mast cells are key components of the skin microenvironment in psoriasis, yet their functional role in this T-cell-mediated inflammatory disorder remains to be elucidated.,To define the impact of T-cell/mast-cell cognate interactions on the cytokines produced by TH cells.,We used human primary mast cells and effector/memory CD4(+) T cells for in vitro coculture experiments, and we analyzed TH cells responses by using cytometry. CD4(+) T-cell/mast-cell conjugates in skin lesions from patients with psoriasis were analyzed by using 3-color immunohistochemistry and confocal microscopy.,We show that IFN-γ-primed human mast cells formed productive immunologic synapses with antigen-experienced CD4(+) T cells. These interactions promoted the generation of TH22 and IL-22/IFN-γ-producing TH cells from the circulating memory CD4(+) T-cell pool via a TNF-α/IL-6-dependent mechanism. An analysis of human psoriatic skin biopsies showed a rich infiltrate of IL-22(+)CD4(+) T cells frequently found in contact with mast cells. Moreover, most of these mast-cell-conjugated lymphocytes coexpressed IFN-γ, suggesting that IL-22(+)IFN-γ(+) CD4(+) T cells are generated in vivo on interaction with mast cells.,Our findings identify human mast cells as functional partners of TH cells, shaping their responses toward IL-22 production.
语言:: eng
DOI:: 10.1016/j.jaci.2013.01.029

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