Exosomes from Thymic Stromal Lymphopoietin-Activated Dendritic Cells Promote Th2 Differentiation through the OX40 Ligand

Abstract

Objectives: Exosomes are extracellular vesicles released from various inflammatory cells, such as T cells, B cells, dendritic cells (DCs), and mast cells, which have been implicated in the modulation of immune response in asthma. This study aimed to investigate whether exosomes from DCs activated by thymic stromal lymphopoietin (TSLP) play a role in T-helper cell differentiation through the OX40 ligand (OX40L). Methods: Serum samples from patients with asthma were collected to measure the levels of OX40L, T-helper type 1 (Th1) cytokine interferon (IFN)-γ, and T-helper type 2 (Th2) cytokine interleukin (IL)-4 by enzyme-linked immunosorbent assay (ELISA). Exosomes were isolated from TSLP-activated DCs and co-cultured with CD4+ T cells. Western blot and ELISA assays were used to measure the levels of OX40L, IFN-γ, and IL-4 in DCs and CD4+ T cells. Flow cytometry was applied to detect Th1 and Th2 cells. Results: OX40L and IL-4 were increased and IFN-γ was decreased in serum from asthmatic patients compared with healthy controls. TSLP induced DCs to express OX40L in released exosomes, which could promote proliferation of CD4+ T cells, elevate the level of IL-4, and promote Th2 differentiation. Conclusion: Blockade of OX40L in DC-derived exosomes could inhibit exosome-mediated CD4+ T proliferation and Th2 differentiation.

Functions of Exosomes in the Triangular Relationship between the Tumor, Inflammation, and Immunity in the Tumor Microenvironment

“…The first release of the exosome database included 58,330 circRNAs, 15,501 lncRNAs, and 18,333 mRNAs, which suggests a sophisticated genetic control system [13]. These functional RNAs can affect biological activities and modulate cellular events such as cell proliferation, apoptosis, differentiation, and immunoregulation [14–16].…”

Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?

“…Exosomes contain various types of molecules, such as lipids, proteins, lipid rafts, mRNAs, miRNAs, and other non-coding RNAs, such as long non-coding RNAs (lncRNAs) (Zhang et al, 2015). Various cell types can release exosomes, such as reticulocytes (Pan and Johnstone, 1983;Diaz-Varela et al, 2018), dendritic cells (Morelli et al, 2004;Huang et al, 2019), B cells (Benjamin et al, 2019, mast cells (Xie et al, 2018), T cells , epithelial cells (Lv et al, 2019), and tumor cells (McAtee et al, 2019).…”

Extracellular Vesicles as Mediators of Cellular Cross Talk in the Lung Microenvironment

“…Most knowledge on lung-resident DCs is based on the development of asthma, where they play a pivotal role in establishing an allergen-specific Th2 response in the airways after stimulation with epithelial alarmins (62). A recent study showed that DCs stimulated in vitro with the epithelial alarmin thymic stromal lymphopoietin secrete EVs expressing OX40L on their surface, via which they stimulate the proliferation of CD4 T cells and Th2 differentiation (63). Furthermore, EVs secreted by monocyte-derived DCs purified from human airways express HLA-DR, MHC-I molecules, CD63, CD86, and CD54, suggesting their potential to cross-present antigen-loaded MHC molecules mediating co-stimulation (21).…”