Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis.
BACKGROUND
Sarcoidosis is a systemic disease of unknown aetiology characterised by granuloma formation and the presence of interferon γ (IFNγ)-producing T cells that cause inflammation and tissue damage in multiple organs, especially the lung. Exosomes are nano-sized immunomodulatory vesicles of endosomal origin released from a diverse range of cells and are also found in physiological fluids including bronchoalveolar lavage fluid (BALF) from healthy individuals.


OBJECTIVE
To investigate whether exosomes are enriched in the lungs of patients with sarcoidosis compared with healthy individuals and whether they could contribute to pathogenesis.


METHODS
BALF exosomes from patients with sarcoidosis (n=36) and healthy controls (n=14) were compared by electron microscopy, flow cytometry, western blot analysis and mass spectrometry. BALF exosomes were incubated with autologous peripheral blood mononuclear cells (PBMCs) or the human bronchial epithelial cell line 16HBE14o-. Cytokines were measured by ELISPOT and ELISA.


RESULTS
BALF from patients with sarcoidosis showed increased levels of exosomes compared with healthy individuals. Exosomes from patients showed significantly higher expression of MHC class I and II, tetraspanins CD9, CD63 and CD81 as well as neuregulin-1, known to be associated with cancer progression. Furthermore, BALF exosomes from patients induced significantly higher IFNγ and interleukin (IL)-13 production in autologous PBMCs compared with healthy individuals and could also stimulate IL-8 production from epithelial cells.


CONCLUSIONS
The results indicate for the first time a role for exosomes in human lung disease with possible contributions to the initiation and progression of inflammation in sarcoidosis. This suggests that exosomes may be a new potential target for the clinical treatment of lung diseases.
Qazi
Khaleda R
KR
Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Torregrosa Paredes
Patricia
P
Dahlberg
Benita
B
Grunewald
Johan
J
Eklund
Anders
A
Gabrielsson
Susanne
S
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000378:metabolism; D055354:Exosomes / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000032:analysis; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
D016207:Cytokines; D018836:Inflammation Mediators; D016209:Interleukin-8; D011506:Proteins