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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
Abstract
Background: Impaired regulatory T cell (Treg) function is thought to contribute to ongoing inflammatory responses in sarcoidosis, but underlying mechanisms remain unclear. Moreover, it is not known if increased apoptotic susceptibility of Tregs may contribute to an impaired immunosuppressive function in sarcoidosis. Therefore, the aim of this study is to analyze proportions, phenotype, survival, and apoptotic susceptibility of Tregs in sarcoidosis. Methods: Patients with pulmonary sarcoidosis (n = 58) were included at time of diagnosis. Tregs were analyzed in broncho-alveolar lavage fluid and peripheral blood of patients and healthy controls (HC). Results: In sarcoidosis patients no evidence was found for a relative deficit of Tregs, neither locally nor systemically. Rather, increased proportions of circulating Tregs were observed, most prominently in patients developing chronic disease. Sarcoidosis circulating Tregs displayed adequate expression of FoxP3, CD25 and CTLA4. Remarkably, in sarcoidosis enhanced CD95 expression on circulating activated CD45RO(+) Tregs was observed compared with HC, and proportions of these cells were significantly increased. Specifically sarcoidosis Tregs - but not Th cells - showed impaired survival compared with HC. Finally, CD95L-mediated apoptosis was enhanced in sarcoidosis Tregs. Conclusion: In untreated patients with active pulmonary sarcoidosis, Tregs show impaired survival and enhanced apoptotic susceptibility towards CD95L. Increased apoptosis likely contributes to the insufficient immunosuppressive function of sarcoidosis Tregs. Further research into this field will help determine whether improvement of Treg survival holds a promising new therapeutic approach for chronic sarcoidosis patients.
Keywords
TNF-ALPHA THERAPY, RHEUMATOID-ARTHRITIS, GRANULOMA-FORMATION, EXPRESSION, LYMPHOCYTES, APOPTOSIS, POPULATION, ACTIVATION, REVERSAL, SYSTEMIC-LUPUS-ERYTHEMATOSUS

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Citation

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

Chicago
Broos, Caroline E, Menno van Nimwegen, Alex Kleinjan, Bregje ten Berge, Femke Muskens, Johannes CCM In’t Veen, Jouke T Annema, et al. 2015. “Impaired Survival of Regulatory T Cells in Pulmonary Sarcoidosis.” Respiratory Research 16.
APA
Broos, C. E., van Nimwegen, M., Kleinjan, A., ten Berge, B., Muskens, F., In’t Veen, J. C., Annema, J. T., et al. (2015). Impaired survival of regulatory T cells in pulmonary sarcoidosis. RESPIRATORY RESEARCH, 16.
Vancouver
1.
Broos CE, van Nimwegen M, Kleinjan A, ten Berge B, Muskens F, In’t Veen JC, et al. Impaired survival of regulatory T cells in pulmonary sarcoidosis. RESPIRATORY RESEARCH. 2015;16.
MLA
Broos, Caroline E et al. “Impaired Survival of Regulatory T Cells in Pulmonary Sarcoidosis.” RESPIRATORY RESEARCH 16 (2015): n. pag. Print.
@article{6973364,
  abstract     = {Background: Impaired regulatory T cell (Treg) function is thought to contribute to ongoing inflammatory responses in sarcoidosis, but underlying mechanisms remain unclear. Moreover, it is not known if increased apoptotic susceptibility of Tregs may contribute to an impaired immunosuppressive function in sarcoidosis. Therefore, the aim of this study is to analyze proportions, phenotype, survival, and apoptotic susceptibility of Tregs in sarcoidosis.
Methods: Patients with pulmonary sarcoidosis (n = 58) were included at time of diagnosis. Tregs were analyzed in broncho-alveolar lavage fluid and peripheral blood of patients and healthy controls (HC).
Results: In sarcoidosis patients no evidence was found for a relative deficit of Tregs, neither locally nor systemically. Rather, increased proportions of circulating Tregs were observed, most prominently in patients developing chronic disease. Sarcoidosis circulating Tregs displayed adequate expression of FoxP3, CD25 and CTLA4. Remarkably, in sarcoidosis enhanced CD95 expression on circulating activated CD45RO(+) Tregs was observed compared with HC, and proportions of these cells were significantly increased. Specifically sarcoidosis Tregs - but not Th cells - showed impaired survival compared with HC. Finally, CD95L-mediated apoptosis was enhanced in sarcoidosis Tregs.
Conclusion: In untreated patients with active pulmonary sarcoidosis, Tregs show impaired survival and enhanced apoptotic susceptibility towards CD95L. Increased apoptosis likely contributes to the insufficient immunosuppressive function of sarcoidosis Tregs. Further research into this field will help determine whether improvement of Treg survival holds a promising new therapeutic approach for chronic sarcoidosis patients.},
  articleno    = {108},
  author       = {Broos, Caroline E and van Nimwegen, Menno and Kleinjan, Alex and ten Berge, Bregje and Muskens, Femke and In't Veen, Johannes CCM and Annema, Jouke T and Lambrecht, Bart and Hoogsteden, Henk C and Hendriks, Rudy W and Kool, Mirjam and van den Blink, Bernt},
  issn         = {1465-993X},
  journal      = {RESPIRATORY RESEARCH},
  keywords     = {TNF-ALPHA THERAPY,RHEUMATOID-ARTHRITIS,GRANULOMA-FORMATION,EXPRESSION,LYMPHOCYTES,APOPTOSIS,POPULATION,ACTIVATION,REVERSAL,SYSTEMIC-LUPUS-ERYTHEMATOSUS},
  language     = {eng},
  pages        = {11},
  title        = {Impaired survival of regulatory T cells in pulmonary sarcoidosis},
  url          = {http://dx.doi.org/10.1186/s12931-015-0265-8},
  volume       = {16},
  year         = {2015},
}

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