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J Allergy Clin Immunol. 2013 May;131(5):1400-7.e11. doi: 10.1016/j.jaci.2013.01.029. Epub 2013 Mar 19.

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

Author information

1
Institut National de la Santé et de la Recherche Médicale, Université de Toulouse, Toulouse, France.

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-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.

PMID:
23518141
DOI:
10.1016/j.jaci.2013.01.029
[Indexed for MEDLINE]

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