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J Allergy Clin Immunol. 2013 Dec;132(6):1314-21. doi: 10.1016/j.jaci.2013.06.010. Epub 2013 Jul 31.

Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3.

Author information

1
Division of Geriatrics, Center for Medical Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Upper Airways Research Laboratory, ENT Department, Ghent University, Ghent, Belgium.

Abstract

BACKGROUND:

In patients with persistent upper airway inflammation, the number of forkhead box protein 3 (Foxp3)(+) regulatory T (Treg) cells is reduced, but the regulation of Foxp3 expression in Treg cells is poorly understood.

OBJECTIVE:

We investigated the interaction between suppressor of cytokine signaling 3 (SOCS3) and Foxp3 expression in the airway mucosa.

METHODS:

Expression of SOCS3 and Foxp3 was measured in tissue from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and control tissue. Coexpression of SOCS3 and Foxp3 was evaluated in PBMCs and in tissue from patients with CRSwNP. We also switched off and overexpressed SOCS3 in tissue from patients with CRSwNP and in pancreatic carcinoma epithelial-like cell line (PANC-1) cells and examined the effect on Foxp3 expression.

RESULTS:

SOCS3 gene and protein expression was upregulated in inflammatory cells in airway mucosa, whereas Foxp3 gene and protein expression was downregulated. Mucosal Treg cells coexpressed both proteins. Switching off the expression of SOCS3 in human airway mucosa resulted in Foxp3 upregulation, whereas inducing it in PANC-1 cells led to Foxp3 downregulation. We also found that phosphorylation of signal transducer and activator of transcription (STAT) 3 was decreased in inflamed mucosa, and we hypothesized that SOCS3 was responsible. Phosphorylation of STAT3 increased on silencing SOCS3 expression in inflamed mucosa and decreased on SOCS3 plasmid transfection in PANC-1 cells.

CONCLUSION:

For the first time, we demonstrate that SOCS3 and Foxp3 are coexpressed in Treg cells in human nasal mucosa and that SOCS3 negatively regulates Foxp3 expression in human airway mucosa, possibly through phosphorylation of STAT3. Hence SOCS3 could be a potential target for restoring Foxp3 expression in Treg cells in patients with persistent mucosal inflammation.

KEYWORDS:

APC; Antigen-presenting cell; CRSwNP; Chronic rhinosinusitis with nasal polyps; Forkhead box protein 3; Foxp3; JAK; Janus kinase; PANC-1; Pancreatic carcinoma epithelial-like cell line; Phosphorylated signal transducer and activator of transcription; Regulatory T; SOCS3; STAT; Signal transducer and activator of transcription; Small interfering RNA; Suppressor of cytokine signaling 3; Treg; airway disease; nasal polyps; pSTAT; siRNA; signal transducer and activator of transcription 3; suppressor of cytokine signaling 3

PMID:
23910692
DOI:
10.1016/j.jaci.2013.06.010
[Indexed for MEDLINE]

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