Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis

Abstract

Background Sarcoidosis is a systemic disease of unknown aetiology characterised by granuloma formation and the presence of interferon g (IFNg)-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 (n¼36) and healthy controls (n¼14) 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.

Proteomics and Pathway Analyses of the Milk Fat Globule in Sheep Naturally Infected by Mycoplasma agalactiae Provide Indications of the In Vivo Response of the Mammary Epithelium to Bacterial Infection

“…This could explain in part why IPA analysis of our data generated a significant score for respiratory disease in the category of diseases and disorders and might underline similarities in the host responses elicited by mycoplasmas upon epithelial tissue infection in different hosts, as well as pointing out common traits in the innate immune response mechanisms elicited in different secretory epithelia. It is intriguing that the respiratory epithelium (20,32) and many other secretory epithelia are increasingly being reported to produce exosomes involved in innate defense and immunomodulation (33,49), such as biliary duct cells (47), intestinal epithelial cells (48), and most interestingly, the human mammary gland (3). Since sheep MFGs present many of the physicochemical attributes and proteomic signatures of exosomes (25,31), functions associated with these secretory vesicles might likely be observed in MFGs during infection of the mammary gland.…”

The Functional Importance of Tetraspanins in Exosomes

“…They also suggest that IL8 upregulation on epithelial cells may follow a different pathway, where TNFα-expressing exosomes have been reported to induce IL8 production [194,181] and CD9 has been described to promote TNFα production via TLR4 signaling [37]. The authors conclude that exosomes contribute to the pathogenesis of this autoimmune disease, which should be taken into account in treatment strategies [194]. DC are the main APCs.…”

“…They noted that exosomes from patients with sarcoidosis differ significantly from exosomes of healthy donors expressing upregulated levels of MHC I and II, HSP70, neuregulin, CD9, CD63, and CD81. Exosomes stimulated IFNγ and IL13 production by leukocytes and IL8 production by epithelial cells [194]. As MHC I and II are associated with tetraspanins, and both MHC molecules and tetraspanins are concomitantly upregulated, the authors argue that the exosomal tetraspanin-MHC complex contributes to the activation of TH1.…”

Quantitative body fluid proteomics in medicine — A focus on minimal invasiveness

“…There are studies regarding exosome analysis of plasma [197], urine [198], amniotic fluid [199], saliva [200], bronchoalveolar lavage fluid [201], breast milk [202] etc.…”