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Evidence for local dendritic cell activation in pulmonary sarcoidosis

Bregje Ten Berge, Alex KleinJan, Femke Muskens, Hamida Hammad UGent, Henk C Hoogsteden, Rudi W Hendriks, Bart Lambrecht UGent and Bernt Van den Blink (2012) RESPIRATORY RESEARCH. 13.
abstract
Background: Sarcoidosis is a granulomatous disease characterized by a seemingly exaggerated immune response against a difficult to discern antigen. Dendritic cells (DCs) are pivotal antigen presenting cells thought to play an important role in the pathogenesis. Paradoxically, decreased DC immune reactivity was reported in blood samples from pulmonary sarcoidosis patients. However, functional data on lung DCs in sarcoidosis are lacking. We hypothesized that at the site of disease DCs are mature, immunocompetent and involved in granuloma formation. Methods: We analyzed myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in broncho-alveolar lavage (BAL) and blood from newly diagnosed, untreated pulmonary sarcoidosis patients and healthy controls using 9-color flowcytometry. DCs, isolated from BAL using flowcytometric sorting (mDCs) or cultured from monocytes (mo-DCs), were functionally assessed in a mixed leukocyte reaction with naive allogeneic CD4+ T cells. Using Immunohistochemistry, location and activation status of CD11c(+)DCs was assessed in mucosal airway biopsies. Results: mDCs in BAL, but not in blood, from sarcoidosis patients were increased in number when compared with mDCs from healthy controls. mDCs purified from BAL of sarcoidosis patients induced T cell proliferation and differentiation and did not show diminished immune reactivity. Mo-DCs from patients induced increased TNF alpha release in co-cultures with naive allogeneic CD4(+) T cells. Finally, immunohistochemical analyses revealed increased numbers of mature CD86(+) DCs in granuloma-containing airway mucosal biopsies from sarcoidosis patients. Conclusion: Taken together, these finding implicate increased local DC activation in granuloma formation or maintenance in pulmonary sarcoidosis.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
Granuloma, TNF alpha, Bronchoalveolar lavage, Dendritic cells, Sarcoidosis, TUMOR-NECROSIS-FACTOR, T-CELLS, ALVEOLAR MACROPHAGES, DISEASE-ACTIVITY, HUMAN LUNG, POLYMORPHISMS, INVOLVEMENT, EXPRESSION, CD4(+), EXCESS
journal title
RESPIRATORY RESEARCH
Respir. Res.
volume
13
article_number
33
pages
12 pages
Web of Science type
Article
Web of Science id
000304059300001
JCR category
RESPIRATORY SYSTEM
JCR impact factor
3.642 (2012)
JCR rank
8/50 (2012)
JCR quartile
1 (2012)
ISSN
1465-993X
DOI
10.1186/1465-9921-13-33
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
2153296
handle
http://hdl.handle.net/1854/LU-2153296
date created
2012-06-14 11:55:10
date last changed
2012-06-20 11:35:32
@article{2153296,
  abstract     = {Background: Sarcoidosis is a granulomatous disease characterized by a seemingly exaggerated immune response against a difficult to discern antigen. Dendritic cells (DCs) are pivotal antigen presenting cells thought to play an important role in the pathogenesis. Paradoxically, decreased DC immune reactivity was reported in blood samples from pulmonary sarcoidosis patients. However, functional data on lung DCs in sarcoidosis are lacking. We hypothesized that at the site of disease DCs are mature, immunocompetent and involved in granuloma formation.
Methods: We analyzed myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in broncho-alveolar lavage (BAL) and blood from newly diagnosed, untreated pulmonary sarcoidosis patients and healthy controls using 9-color flowcytometry. DCs, isolated from BAL using flowcytometric sorting (mDCs) or cultured from monocytes (mo-DCs), were functionally assessed in a mixed leukocyte reaction with naive allogeneic CD4+ T cells. Using Immunohistochemistry, location and activation status of CD11c(+)DCs was assessed in mucosal airway biopsies.
Results: mDCs in BAL, but not in blood, from sarcoidosis patients were increased in number when compared with mDCs from healthy controls. mDCs purified from BAL of sarcoidosis patients induced T cell proliferation and differentiation and did not show diminished immune reactivity. Mo-DCs from patients induced increased TNF alpha release in co-cultures with naive allogeneic CD4(+) T cells. Finally, immunohistochemical analyses revealed increased numbers of mature CD86(+) DCs in granuloma-containing airway mucosal biopsies from sarcoidosis patients.
Conclusion: Taken together, these finding implicate increased local DC activation in granuloma formation or maintenance in pulmonary sarcoidosis.},
  articleno    = {33},
  author       = {Ten Berge, Bregje and KleinJan, Alex and Muskens, Femke and Hammad, Hamida and Hoogsteden, Henk C and Hendriks, Rudi W and Lambrecht, Bart and Van den Blink, Bernt},
  issn         = {1465-993X},
  journal      = {RESPIRATORY RESEARCH},
  keyword      = {Granuloma,TNF alpha,Bronchoalveolar lavage,Dendritic cells,Sarcoidosis,TUMOR-NECROSIS-FACTOR,T-CELLS,ALVEOLAR MACROPHAGES,DISEASE-ACTIVITY,HUMAN LUNG,POLYMORPHISMS,INVOLVEMENT,EXPRESSION,CD4(+),EXCESS},
  language     = {eng},
  pages        = {12},
  title        = {Evidence for local dendritic cell activation in pulmonary sarcoidosis},
  url          = {http://dx.doi.org/10.1186/1465-9921-13-33},
  volume       = {13},
  year         = {2012},
}

Chicago
Ten Berge, Bregje, Alex KleinJan, Femke Muskens, Hamida Hammad, Henk C Hoogsteden, Rudi W Hendriks, Bart Lambrecht, and Bernt Van den Blink. 2012. “Evidence for Local Dendritic Cell Activation in Pulmonary Sarcoidosis.” Respiratory Research 13.
APA
Ten Berge, Bregje, KleinJan, A., Muskens, F., Hammad, H., Hoogsteden, H. C., Hendriks, R. W., Lambrecht, B., et al. (2012). Evidence for local dendritic cell activation in pulmonary sarcoidosis. RESPIRATORY RESEARCH, 13.
Vancouver
1.
Ten Berge B, KleinJan A, Muskens F, Hammad H, Hoogsteden HC, Hendriks RW, et al. Evidence for local dendritic cell activation in pulmonary sarcoidosis. RESPIRATORY RESEARCH. 2012;13.
MLA
Ten Berge, Bregje, Alex KleinJan, Femke Muskens, et al. “Evidence for Local Dendritic Cell Activation in Pulmonary Sarcoidosis.” RESPIRATORY RESEARCH 13 (2012): n. pag. Print.