Advanced search
1 file | 2.13 MB

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

Feng Lan (UGent) , Nan Zhang (UGent) , Jie Zhang, Olga Krysko (UGent) , Quanbo Zhang, Junming Xian, Lara Derycke (UGent) , Yanyu Qi, Kai Li, Shixi Liu, et al.
Author
Organization
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
suppressor of cytokine signaling 3, Forkhead box protein 3, signal transducer and activator of transcription 3, airway disease, nasal polyps, EXPERIMENTAL ALLERGIC-ASTHMA, VERSUS-HOST-DISEASE, SOCS PROTEINS, FOXP3 EXPRESSION, SINUS DISEASE, INFLAMMATION, RESPONSES, GENERATION, MECHANISM, EXPANSION

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 2.13 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Lan, Feng, Nan Zhang, Jie Zhang, Olga Krysko, Quanbo Zhang, Junming Xian, Lara Derycke, et al. 2013. “Forkhead Box Protein 3 in Human Nasal Polyp Regulatory T Cells Is Regulated by the Protein Suppressor of Cytokine Signaling 3.” Journal of Allergy and Clinical Immunology 132 (6): 1314–1321.
APA
Lan, Feng, Zhang, N., Zhang, J., Krysko, O., Zhang, Q., Xian, J., Derycke, L., et al. (2013). Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 132(6), 1314–1321.
Vancouver
1.
Lan F, Zhang N, Zhang J, Krysko O, Zhang Q, Xian J, et al. Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2013;132(6):1314–21.
MLA
Lan, Feng, Nan Zhang, Jie Zhang, et al. “Forkhead Box Protein 3 in Human Nasal Polyp Regulatory T Cells Is Regulated by the Protein Suppressor of Cytokine Signaling 3.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 132.6 (2013): 1314–1321. Print.
@article{4290685,
  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.},
  author       = {Lan, Feng and Zhang, Nan and Zhang, Jie and Krysko, Olga and Zhang, Quanbo and Xian, Junming and Derycke, Lara and Qi, Yanyu and Li, Kai and Liu, Shixi and Lin, Ping and Bachert, Claus},
  issn         = {0091-6749},
  journal      = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
  language     = {eng},
  number       = {6},
  pages        = {1314--1321},
  title        = {Forkhead box protein 3 in human nasal polyp regulatory T cells is regulated by the protein suppressor of cytokine signaling 3},
  url          = {http://dx.doi.org/10.1016/j.jaci.2013.06.010},
  volume       = {132},
  year         = {2013},
}

Altmetric
View in Altmetric
Web of Science
Times cited: