Epithelial exosomal contactin-1 promotes monocyte-derived dendritic cell–dominant T-cell responses in asthma

Zhang, Meng; Yu, Qianying; Tang, Wei; Wu, Yujiao; Lv, Jiajia; Sun, Limin; Shi, Guochao; Wu, Min; Qu, Jieming; Di, Caixia; Xia, Zhenwei

doi:10.1016/j.jaci.2021.04.025

Cited by 37 publications

(38 citation statements)

References 46 publications

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“…These results prompt us to speculate that DCEVs may carry HDM antigenic components, consistent with our previous study demonstrating that EXOs derived from HDM-treated airway epithelial cells contain some peptides and proteins specific to mites and promote allergic airway inflammation in mice models of asthma. 38 In comparison, sensitization with DCEVs stimulated with both HDM and hemin failed to induce allergic airway inflammation.…”

Section: Discussionmentioning

confidence: 97%

Hemin-primed dendritic cells suppress allergic airway inflammation through releasing extracellular vesicles

Zhang

et al. 2021

Journal of Leukocyte Biology

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Hemin, a substrate of heme oxygenase (HO)-1, induces HO-1 expression on a variety of cells to exert anti-oxidant and anti-inflammatory roles. However, the role of HO-1 in allergic diseases for dendritic cells (DCs) is not fully understood. Here, we report that HO-1 modulates asthmatic airway inflammation by hemin-treated DC-released extracellular vesicles (DCEVs). Following induction of bone marrow-derived DCs by hemin and then by house dust mite (HDM) in vitro, mouse CD4+ naïve T cells were cocultured with DCEVs to determine T helper (h) cell differentiation. C57BL/6 mice were sensitized by different stimuli-induced DCEVs and challenged with HDM to analyze the changes of inflammatory cells and cytokines in the lung and bronchoalveolar lavage fluid. The results showed that hemin-treated DCEVs (hemin-DCEVs) express phosphatidylserine (PS), CD81, heat shock protein 70, and HO-1, which facilitates regulatory T (Treg) cells differentiation in vitro and in vivo. In HDM-induced asthmatic mouse model, hemin-DCEVs inhalation reduced eosinophils infiltration and mucus secretion in the airway, decreased the levels of IL-4, IL-5, and IL-13 in the lung and the number of Th2 cells in mediastinal lymph nodes (MLNs), and increased the number of Treg cells in MLNs. Thus, our study demonstrated, for the first time, that EVs from HO-1overexpressing DCs alleviate allergic airway inflammation of eosinophilic asthma by potentiating Treg cells differentiation and limiting proinflammatory cytokine secretion, which expands our understanding of HO-1 function, opening the door for HO-1 inducer-like hemin as a novel therapeutic strategy for asthma or other allergic diseases.

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Section: Discussionmentioning

confidence: 97%

Hemin-primed dendritic cells suppress allergic airway inflammation through releasing extracellular vesicles

Zhang

et al. 2021

Journal of Leukocyte Biology

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“…Upon allergen exposure, exosomes released from epithelial cells induce the proliferation and the chemotaxis of macrophages during asthmatic inflammation [74]. Recently, a study showed that in epithelial exosomes, contactin-1 (CNTN1) is involved in the activation and recruitment of monocyte-derived dendritic cells and T-cell responses in allergic asthma [75]. Likewise, eosinophil-derived exosomes promote eosinophil migration, augment adhesion by a specific increase of adhesion molecules, such as ICAM-1 and induce reactive oxygen species (ROS) and nitric oxide (NO) production in an autocrine fashion [76].…”

Section: Exosomes In Allergic Sensitization and Inflammationmentioning

confidence: 99%

“…Thus, mast cell-derived exosomes specifically or exosomes engineered to express FcεRI are very attractive candidates for the engineering of novel therapeutic strategies in allergy due to their effect as an anti-IgE agent. Additionally, epithelial cells release exosomes containing contactin-1 (CNTN1) that play a role in recruiting macrophages and mo-DCs [75]. DC-derived and B cell-derived exosomes containing allergen, p-MHCII complexes and co-stimulatory molecules can amplify the TH2 milieu [66,81].…”

Section: The Therapeutic Potential Of Mast Cell-derived Exosomesmentioning

confidence: 99%

“…Allergic sensitization is thought to be driven by allergen entry through epithelium in a damaged or inflamed environment. Epithelial cells release TSLP/IL-33/IL-25 activating DCs and ILC2 cells which initiate type 2 immunity (TH2).Additionally, epithelial cells release exosomes containing contactin-1 (CNTN1) that play a role in recruiting macrophages and mo-DCs[75]. DC-derived and B cell-derived exosomes containing allergen, p-MHCII complexes and co-stimulatory molecules can amplify the TH2 milieu[66,81].…”

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confidence: 99%

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The Potential of Exosomes in Allergy Immunotherapy

Engeroff

Vogel

2022

Vaccines

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Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation, and we discuss the mechanisms by which exosomes could potentially be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: a) Mast cell-derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. c) Exosomes could promote TH1-like responses towards an allergen. d) Exosomes could modulate IgE-facilitated antigen presentation.

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“…gel-forming mucins (180), complement component C3, SERPIN3. The addition of an allergen source (house dust mite; HDM) to the AEC culture resulted in DC activation by secreted sEVs in vitro and increased airway inflammation in a murine model (181); the role for contactin-1 has been demonstrated. Furthermore, it has been also demonstrated that sEVs may be a vehicle of secretion for an important Th2-promoting cytokine, interleukin 33 (IL-33); the cytokine seams to decorate the EV surface rather than be included within the intraluminal cargo (182).…”

Section: Asthmamentioning

confidence: 99%

The Role of Non-Immune Cell-Derived Extracellular Vesicles in Allergy

2021

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Extracellular vesicles (EVs), and especially exosomes, have been shown to mediate information exchange between distant cells; this process directly affects the biological characteristics and functionality of the recipient cell. As such, EVs significantly contribute to the shaping of immune responses in both physiology and disease states. While vesicles secreted by immune cells are often implicated in the allergic process, growing evidence indicates that EVs from non-immune cells, produced in the stroma or epithelia of the organs directly affected by inflammation may also play a significant role. In this review, we provide an overview of the mechanisms of allergy to which those EVs contribute, with a particular focus on small EVs (sEVs). Finally, we also give a clinical perspective regarding the utilization of the EV-mediated communication route for the benefit of allergic patients.

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Epithelial exosomal contactin-1 promotes monocyte-derived dendritic cell–dominant T-cell responses in asthma

Cited by 37 publications

References 46 publications

Hemin-primed dendritic cells suppress allergic airway inflammation through releasing extracellular vesicles

Hemin-primed dendritic cells suppress allergic airway inflammation through releasing extracellular vesicles

The Potential of Exosomes in Allergy Immunotherapy

The Role of Non-Immune Cell-Derived Extracellular Vesicles in Allergy

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