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 T_H cells.

We used human primary mast cells and effector/memory CD4⁺ T cells for in vitro coculture experiments, and we analyzed T_H 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 T_H22 and IL-22/IFN-γ–producing T_H cells from the circulating memory CD4⁺ T-cell pool via a TNF-⍺/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 T_H cells, shaping their responses toward IL-22 production.