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Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis
  1. Khaleda R Qazi1,
  2. Patricia Torregrosa Paredes1,
  3. Benita Dahlberg2,
  4. Johan Grunewald2,
  5. Anders Eklund2,
  6. Susanne Gabrielsson1
  1. 1Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden
  2. 2Department of Medicine, Division of Respiratory Medicine, Lung Research Laboratory, Karolinska Hospital, Stockholm, Sweden
  1. Correspondence to Associate Professor Susanne Gabrielsson, Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet and University Hospital, KS L2:04, SE-171 76 Stockholm, Sweden; susanne.gabrielsson{at}ki.se

Abstract

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.

Design 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.

Conclusion 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.

  • Exosomes
  • sarcoidosis
  • bronchoalveolar lavage fluid
  • neuregulin
  • interleukin-8
  • innate immunity
  • lymphocyte biology
  • systemic disease and lungs

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Footnotes

  • Linked articles 138438.

  • KRQ and PTP share first authorship of the paper.

  • Funding This study was supported by grants from the Karolinska Institutet, the Swedish Medical Research Council (no 15242-05-2), the Torsten and Ragnar Söderbergs Foundation, the Stockholm County Council, the Mats Kleberg Foundation, the King Oscar II Jubilee Foundation, the Swedish Cancer Foundation (no. 08 0299), the Swedish Heart-Lung Foundation, the Swedish Society of Medicine, the Centre for Allergy Research Karolinska Institutet, the Swedish Cancer and Allergy Foundation and the Swedish Asthma and Allergy Association's Research Foundation.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the local ethics committee of Northern Stockholm.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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