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

Abstract

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.

Keywords: allergic rhinitis; allergy; asthma; atopic dermatitis; cellular communication; exosomes; extracellular vesicles; immune responses.

Figure 1

Different types and biogenesis of extracellular vesicles. Two types of EVs form through outward invagination of the plasma membrane; microvesicles and apoptotic bodies. The apoptotic bodies are larger and form in the context of programmed cell death; they enclose organelles removed from the cell during degradation, while microvesicles are produced by a healthy cell; their content is similar to that of the cytoplasm. Secreted midbody remnant is also secreted from the plasma membrane, but contain residual secreted midbody remnants are following cell division. In contrast to this, exosomes form through a distinct cellular pathway and within the endocytic system where inward budding of late endosome leads to the formation of a multivesicular body containing multiple intraluminal vesicles. The content of multivesicular bodies is either digested after fusion with lysosome (degradative pathway) or released into the extracellular space (secretory pathway). EE, early endosome; LE, late endosome; MVB, multivesicular body; ILVs, intraluminal vesicles; sMB-R, secreted midbody remnant.

Figure 2

Involvement of non-immune cell-secreted extracellular vesicles in immunological processes of innate and adaptive immunity. Extracellular vesicles produced by cells of non-immune origin participate in exchange of information that contributes to immune responses. In the innate arm EVs enable passive immunity and may both induce activation and modulate innate cell function. In the adaptive arm EVs may influence antigen presentation, affect dendritic cell differentiation and phenotype; they have also been implicated in T cell polarization into Th or Treg subsets. sEVs, small EVs; m/lEVs, medium/large EVs.

Figure 3

Extracellular vesicles produced by non-immune cells and their involvement in allergic diseases. Microvesicles and exosomes are the two types of extracellular vesicles which have been implicated in the pathogenesis of allergic inflammation. There is significant predominance of the exosomal involvement, likely due to the phenotypic characteristics and physical properties of these vesicles, enabling more without damage and entering the circulation for long-distance delivery. HBECs, human bronchial epithelial cells; BALF, bronchoalveolar lavage fluid; NM, nasal mucus; NECs, nasal epithelial cells; AECs, airway epithelial cells; HTBEs, human tracheobronchial cells; RBCs, red blood cells; IECs, intestinal epithelial cells; KCs, keratinocytes; FBs, fibroblasts; MSCs, mesenchymal stem cells. ↑ increase in a process; ↓ decrease in a process; + disease promoting effect; - disease alleviating effect.