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-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.
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-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.
Authors: Nicolas Gaudenzio; Riccardo Sibilano; Philipp Starkl; Mindy Tsai; Stephen J Galli; Laurent L Reber Journal: J Vis Exp Date: 2015-05-27 Impact factor: 1.355
Authors: Nicolas Gaudenzio; Riccardo Sibilano; Thomas Marichal; Philipp Starkl; Laurent L Reber; Nicolas Cenac; Benjamin D McNeil; Xinzhong Dong; Joseph D Hernandez; Ronit Sagi-Eisenberg; Ilan Hammel; Axel Roers; Salvatore Valitutti; Mindy Tsai; Eric Espinosa; Stephen J Galli Journal: J Clin Invest Date: 2016-09-19 Impact factor: 14.808
Authors: Laurent L Reber; Thomas Marichal; Jeremy Sokolove; Philipp Starkl; Nicolas Gaudenzio; Yoichiro Iwakura; Hajime Karasuyama; Lawrence B Schwartz; William H Robinson; Mindy Tsai; Stephen J Galli Journal: Arthritis Rheumatol Date: 2014-10 Impact factor: 10.995
Authors: Eva Conde; Romain Bertrand; Bianca Balbino; Jonathan Bonnefoy; Julien Stackowicz; Noémie Caillot; Fabien Colaone; Samir Hamdi; Raïssa Houmadi; Alexia Loste; Jasper B J Kamphuis; François Huetz; Laurent Guilleminault; Nicolas Gaudenzio; Aurélie Mougel; David Hardy; John N Snouwaert; Beverly H Koller; Vincent Serra; Pierre Bruhns; Géraldine Grouard-Vogel; Laurent L Reber Journal: Nat Commun Date: 2021-05-11 Impact factor: 14.919