Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype - 29/04/13
Abstract |
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-⍺/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.
Conclusions |
Our findings identify human mast cells as functional partners of TH cells, shaping their responses toward IL-22 production.
Le texte complet de cet article est disponible en PDF.Key words : Mast cells, TH cells, IL-22, immunologic synapse, inflammation, psoriasis
Abbreviations used : APC, CLA, DC, hMC, hMCIFN-γ, IHC, SAg, SCF
Plan
This study was supported by grants from the Association pour la Recherche sur le Cancer (grant no. SL220100601347) and from Institut National de la Santé et de la Recherche Médicale. |
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Disclosure of potential conflict of interest: All authors have received research support from Association pour la Recherche sur le Cancer and INSERM. |
Vol 131 - N° 5
P. 1400 - mai 2013 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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