Exosomes derived from thymic stromal lymphopoietin-treated dendritic cells regulate T helper 17/regulatory T cell differentiation via miR-21/Smad7 axis

Vaccination is the best prophylaxis for the prevention of infectious diseases, including coronavirus disease 2019. However, the efficacy of vaccines and onset of adverse reactions vary among individuals. Circulating extracellular vesicles (EVs) regulate the immune responses after vaccination by delivering microRNAs (miRNAs) to myeloid and lymphoid cells. Among these, miR-192 levels in serum EVs increase with aging, in an IL-6-dependent manner, reducing excessive IL-6 expression in aged mice, creating a negative feedback loop. Excessive IL-6 expression reduces vaccination efficacy in aged mice, while EV miR-192 improves efficacy in these aged mice as well, making this miRNA an interesting focus of study. miR-21 levels in serum EVs also increase with aging, and regulates the expression of IL-12 required for Th1 responses; therefore, EV miR-21 is expected to regulate vaccine efficacy. miR-451a, another important miRNA, is abundant in serum EVs and controls the expression of cytokines, such as type I interferon and IL-6. However, levels differ among individuals and correlate with local inflammatory symptoms experienced after a seasonal flu vaccination. These findings suggest the importance of EV miRNAs as a tool to improve vaccine efficacy and also as biomarkers to predict the immune response and adverse reactions after vaccinations.

Section: Mir-21 Regulates Immune Responses After Vaccinationmentioning

confidence: 99%

Circulating Extracellular Vesicles Carry Immune Regulatory miRNAs and Regulate Vaccine Efficacy and Local Inflammatory Response After Vaccination

Oshiumi

2021

“…Third, although most miRNAs are conserved between humans and mice, some have opposing roles in human and mouse Th cells. For example, miR-21 ( 181 ) and miR-21-5p ( 194 ) promote Th17 activation in mice, but inhibit Th17 activation in humans ( 177 , 195 ) ( Supplementary Table 4 ). As extensive studies on miRNAs function in Th cells have been conducted in mouse models, more efforts should be made to verify their roles in humans.…”

Section: Discussionmentioning

confidence: 99%

“…also indicated that exosomes derived from thymic stromal lymphopoietin-treated dendritic cells enhance RORγt and IL-17 while repressing Foxp3 and IL-10 expression in CD4 + T cells. Further studies have shown that miR-21 is highly expressed in exosomes and suppresses Smad7 expression, thereby disrupting Treg/Th17 differentiation ( 177 ).…”

Section: Mirnas In the Teff/treg Balancementioning

confidence: 99%

The role of miRNAs in T helper cell development, activation, fate decisions and tumor immunity

Xu,

Chen,

Chang

et al. 2024

T helper (Th) cells are central members of adaptive immunity and comprise the last line of defense against pathogen infection and malignant cell invasion by secreting specific cytokines. These cytokines then attract or induce the activation and differentiation of other immune cells, including antibody-producing B cells and cytotoxic CD8+ T cells. Therefore, the bidirectional communication between Th cells and tumor cells and their positioning within the tumor microenvironment (TME), especially the tumor immune microenvironment (TIME), sculpt the tumor immune landscape, which affects disease initiation and progression. The type, number, and condition of Th cells in the TME and TIME strongly affect tumor immunity, which is precisely regulated by key effectors, such as granzymes, perforins, cytokines, and chemokines. Moreover, microRNAs (miRNAs) have emerged as important regulators of Th cells. In this review, we discuss the role of miRNAs in regulating Th cell mediated adaptive immunity, focusing on the development, activation, fate decisions, and tumor immunity.

“…Extracellular vesicles (EVs)—including exosomes that are wrapped with biological messengers, such as microRNAs and cytokines from DCs and Tregs—can complete cell interactions without direct contact ( 111 , 112 ). Exosomes with membrane-associated TGF-β1 from gene-modified DCs can maintain the inhibitory function of Tregs, reduce the frequency of Th17 cells, and curb the progression of EAE ( 111 , 112 ). Moreover, DC-derived exosomes can promote myelin regeneration ( 113 ).…”

Section: Bidirectional Dc-treg Cell Crosstalk In Ms Patients and Eae ...mentioning

confidence: 99%

Crosstalk between dendritic cells and regulatory T cells: Protective effect and therapeutic potential in multiple sclerosis

Yang

et al. 2022

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system related to autoimmunity and is characterized by demyelination, neuroinflammation, and neurodegeneration. Cell therapies mediated by dendritic cells (DCs) and regulatory T cells (Tregs) have gradually become accumulating focusing in MS, and the protective crosstalk mechanisms between DCs and Tregs provide the basis for the efficacy of treatment regimens. In MS and its animal model experimental autoimmune encephalomyelitis, DCs communicate with Tregs to form immune synapses and complete a variety of complex interactions to counteract the unbalanced immune tolerance. Through different co-stimulatory/inhibitory molecules, cytokines, and metabolic enzymes, DCs regulate the proliferation, differentiation and function of Tregs. On the other hand, Tregs inhibit the mature state and antigen presentation ability of DCs, ultimately improving immune tolerance. In this review, we summarized the pivotal immune targets in the interaction between DCs and Tregs, and elucidated the protective mechanisms of DC-Treg cell crosstalk in MS, finally interpreted the complex cell interplay in the manner of inhibitory feedback loops to explore novel therapeutic directions for MS.