부산대학교 도서관

BACKGROUND:: 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. OBJECTIVE:: To define the impact of T-cell/mast-cell cognate interactions on the cytokines produced by TH cells. METHODS:: 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. RESULTS:: 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-22CD4 T cells frequently found in contact with mast cells. Moreover, most of these mast-cell–conjugated lymphocytes coexpressed IFN-γ, suggesting that IL-22IFN-γ CD4 T cells are generated in vivo on interaction with mast cells. CONCLUSIONS:: Our findings identify human mast cells as functional partners of TH cells, shaping their responses toward IL-22 production.