PMID- 22513006
OWN - NLM
STAT- MEDLINE
DCOM- 20120823
LR  - 20211021
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 13
IP  - 1
DP  - 2012 Apr 18
TI  - Evidence for local dendritic cell activation in pulmonary sarcoidosis.
PG  - 33
LID - 10.1186/1465-9921-13-33 [doi]
AB  - 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 TNFalpha 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.
FAU - Ten Berge, Bregje
AU  - Ten Berge B
AD  - Department of Pulmonary Medicine, Erasmus MC, Dr Molewaterplein 50, 3015 GE 
      Rotterdam, The Netherlands.
FAU - Kleinjan, Alex
AU  - Kleinjan A
FAU - Muskens, Femke
AU  - Muskens F
FAU - Hammad, Hamida
AU  - Hammad H
FAU - Hoogsteden, Henk C
AU  - Hoogsteden HC
FAU - Hendriks, Rudi W
AU  - Hendriks RW
FAU - Lambrecht, Bart N
AU  - Lambrecht BN
FAU - Van den Blink, Bernt
AU  - Van den Blink B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120418
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biopsy
MH  - Bronchoalveolar Lavage Fluid
MH  - Case-Control Studies
MH  - Cell Count
MH  - Cell Proliferation
MH  - Dendritic Cells/immunology/*pathology
MH  - Female
MH  - Granuloma/*pathology
MH  - Humans
MH  - Lung/*pathology
MH  - Male
MH  - Middle Aged
MH  - Myeloid Cells/pathology
MH  - Sarcoidosis, Pulmonary/blood/*pathology
MH  - Young Adult
PMC - PMC3352267
EDAT- 2012/04/20 06:00
MHDA- 2012/08/24 06:00
PMCR- 2012/04/18
CRDT- 2012/04/20 06:00
PHST- 2011/07/09 00:00 [received]
PHST- 2012/04/18 00:00 [accepted]
PHST- 2012/04/20 06:00 [entrez]
PHST- 2012/04/20 06:00 [pubmed]
PHST- 2012/08/24 06:00 [medline]
PHST- 2012/04/18 00:00 [pmc-release]
AID - 1465-9921-13-33 [pii]
AID - 10.1186/1465-9921-13-33 [doi]
PST - epublish
SO  - Respir Res. 2012 Apr 18;13(1):33. doi: 10.1186/1465-9921-13-33.