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Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis

Bregje ten Berge, Marthe S Paats, Ingrid M Bergen, Bernt van den Blink, Henk C Hoogsteden, Bart Lambrecht UGent, Rudi W Hendriks and Alex KleinJan (2012) RHEUMATOLOGY. 51(1). p.37-46
abstract
Objective. Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Although the aetiology is unknown, sarcoidosis is thought to be mediated by Th1 lymphocytes. Recently, IL-17A has been implicated in granuloma formation in various diseases, including tuberculosis. Therefore, we hypothesized that Th17 cells play a role in sarcoidosis, paralleling recent findings in autoimmune diseases such as RA. The aim of our study was to investigate the role of Th17 cells in sarcoidosis. Methods. T cells were investigated by intracellular flow cytometry and immunohistochemistry, in blood, bronchoalveolar lavages (BALs) and bronchial mucosal biopsies from a cohort of newly diagnosed sarcoidosis patients and healthy controls. Results. Circulating memory CD4(+) T-cell populations of sarcoidosis patients contained significantly increased proportions of IL-17A(+) cells when compared with healthy controls. Interestingly, proportions of IL17A/IFN-gamma and IL-17A/IL-4 double-producing cells were significantly increased in blood of sarcoidosis patients and were present in substantial numbers in BAL. In granuloma-containing, but not in non-granulomatous sarcoidosis biopsies, we found significantly increased numbers of IL-17A(+) T cells, located in and around granulomas throughout the lamina propria. IL-22(+) T cells were increased in the subepithelial layer. Conclusions. Enhanced IL-17A expression in granulomas and the presence of IL-17A(+), IL-17A(+) IFN-gamma(+) and IL-17A(+) IL-4(+) memory Th cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction or maintenance in sarcoidosis. Therefore, neutralization of IL-17A activity may be a novel strategy to treat sarcoidosis.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
flow cytometry, granulomas, human, immunohistochemistry, IL-17, IL-22, lung, sarcoidosis, T helper-17 cells, PULMONARY SARCOIDOSIS, TH17 CELLS, RHEUMATOID-ARTHRITIS, IMMUNE-RESPONSE, INTERLEUKIN 22, T(H)17 CELLS, CYTOKINE, DISTINCT, GAMMA, SUBSETS
journal title
RHEUMATOLOGY
Rheumatology
volume
51
issue
1
pages
37 - 46
Web of Science type
Article
Web of Science id
000298383200007
JCR category
RHEUMATOLOGY
JCR impact factor
4.212 (2012)
JCR rank
7/29 (2012)
JCR quartile
1 (2012)
ISSN
1462-0324
DOI
10.1093/rheumatology/ker316
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2004218
handle
http://hdl.handle.net/1854/LU-2004218
date created
2012-01-26 10:37:06
date last changed
2012-03-06 12:14:09
@article{2004218,
  abstract     = {Objective. Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Although the aetiology is unknown, sarcoidosis is thought to be mediated by Th1 lymphocytes. Recently, IL-17A has been implicated in granuloma formation in various diseases, including tuberculosis. Therefore, we hypothesized that Th17 cells play a role in sarcoidosis, paralleling recent findings in autoimmune diseases such as RA. The aim of our study was to investigate the role of Th17 cells in sarcoidosis.
Methods. T cells were investigated by intracellular flow cytometry and immunohistochemistry, in blood, bronchoalveolar lavages (BALs) and bronchial mucosal biopsies from a cohort of newly diagnosed sarcoidosis patients and healthy controls.
Results. Circulating memory CD4(+) T-cell populations of sarcoidosis patients contained significantly increased proportions of IL-17A(+) cells when compared with healthy controls. Interestingly, proportions of IL17A/IFN-gamma and IL-17A/IL-4 double-producing cells were significantly increased in blood of sarcoidosis patients and were present in substantial numbers in BAL. In granuloma-containing, but not in non-granulomatous sarcoidosis biopsies, we found significantly increased numbers of IL-17A(+) T cells, located in and around granulomas throughout the lamina propria. IL-22(+) T cells were increased in the subepithelial layer.
Conclusions. Enhanced IL-17A expression in granulomas and the presence of IL-17A(+), IL-17A(+) IFN-gamma(+) and IL-17A(+) IL-4(+) memory Th cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction or maintenance in sarcoidosis. Therefore, neutralization of IL-17A activity may be a novel strategy to treat sarcoidosis.},
  author       = {ten Berge, Bregje and Paats, Marthe S and Bergen, Ingrid M and van den Blink, Bernt and Hoogsteden, Henk C and Lambrecht, Bart and Hendriks, Rudi W and KleinJan, Alex},
  issn         = {1462-0324},
  journal      = {RHEUMATOLOGY},
  keyword      = {flow cytometry,granulomas,human,immunohistochemistry,IL-17,IL-22,lung,sarcoidosis,T helper-17 cells,PULMONARY SARCOIDOSIS,TH17 CELLS,RHEUMATOID-ARTHRITIS,IMMUNE-RESPONSE,INTERLEUKIN 22,T(H)17 CELLS,CYTOKINE,DISTINCT,GAMMA,SUBSETS},
  language     = {eng},
  number       = {1},
  pages        = {37--46},
  title        = {Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis},
  url          = {http://dx.doi.org/10.1093/rheumatology/ker316},
  volume       = {51},
  year         = {2012},
}

Chicago
ten Berge, Bregje, Marthe S Paats, Ingrid M Bergen, Bernt van den Blink, Henk C Hoogsteden, Bart Lambrecht, Rudi W Hendriks, and Alex KleinJan. 2012. “Increased IL-17A Expression in Granulomas and in Circulating Memory T Cells in Sarcoidosis.” Rheumatology 51 (1): 37–46.
APA
ten Berge, B., Paats, M. S., Bergen, I. M., van den Blink, B., Hoogsteden, H. C., Lambrecht, B., Hendriks, R. W., et al. (2012). Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis. RHEUMATOLOGY, 51(1), 37–46.
Vancouver
1.
ten Berge B, Paats MS, Bergen IM, van den Blink B, Hoogsteden HC, Lambrecht B, et al. Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis. RHEUMATOLOGY. 2012;51(1):37–46.
MLA
ten Berge, Bregje, Marthe S Paats, Ingrid M Bergen, et al. “Increased IL-17A Expression in Granulomas and in Circulating Memory T Cells in Sarcoidosis.” RHEUMATOLOGY 51.1 (2012): 37–46. Print.