Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype

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 T-H 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-gamma-primed human mast cells formed productive immunologic synapses with antigen-experienced CD4(+) T cells. These interactions promoted the generation of T(H)22 and IL-22/IFN-gamma-producing T-H cells from the circulating memory CD4(+) T-cell pool via a TNF-alpha/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-gamma, suggesting that IL-22(+)IFN-gamma(+) 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.