Extracellular Vesicles in Immune Regulation: Mechanisms, Microbiome Interactions, and Therapeutic Potential

Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles secreted by nearly all cell types, and they have emerged as central players in immune regulation. By transferring proteins, lipids, nucleic acids, and metabolites, EVs modulate immune cell signaling, cytokine networks, and pathogen defense mechanisms. Once considered mere waste carriers, EVs are now recognized as critical mediators of immune communication across both innate and adaptive compartments. They influence antigen presentation, T and B cell responses, and the activation of dendritic cells and macrophages, while also serving as vehicles for pathogen-derived signals. In the context of host-microbiome interactions, microbial EVs orchestrate cross-kingdom communication that profoundly impacts mucosal and systemic immunity. Despite remarkable advances, fundamental questions remain regarding EV biogenesis, cargo selection, and how these vesicles shape immune responses in health, infection, and disease. Addressing these gaps is essential for unlocking EVs’ potential as biomarkers, therapeutic targets, and vehicles in immunotherapy.

The goal of this Research Topic is to advance understanding of how extracellular vesicles orchestrate immune regulation and immune–microbiome interactions. EVs represent a key mode of communication within the immune system and between the host and microbes, shaping processes from tolerance to inflammation. Yet, the molecular underpinnings of how EVs influence immune responses remain poorly defined. This collection seeks to showcase innovative studies that uncover immunological mechanisms mediated by EVs, ranging from antigen processing and presentation, modulation of cytokine and chemokine signaling, to shaping immune cell plasticity and cross-talk. A particular emphasis will be placed on the role of microbial and host-derived EVs in infection, vaccination, autoimmunity, and cancer immunology.

By bringing together contributions that integrate cutting-edge omics, imaging, and functional immunology approaches, this Research Topic aims to deepen mechanistic insights and accelerate translational applications. Ultimately, the collection will highlight EVs as emerging regulators of immunity and as powerful tools for developing diagnostics, immunotherapies, and next-generation vaccines.

This Research Topic invites contributions that explore the roles of extracellular vesicles (EVs) in immune regulation and immune–microbiome communication. We welcome original research, reviews, and perspectives in areas such as:
• EV Biogenesis and Cargo in Immunity: Mechanisms of EV formation, molecular cargo selection, and their immunomodulatory roles.
• EVs in Innate and Adaptive Immunity: Effects on antigen presentation, T/B cell responses, cytokine regulation, and immune tolerance.
• Microbial and Host–Microbiome EVs: Cross-kingdom signaling and implications for mucosal and systemic immune responses.
• EVs in Immune Pathogenesis: Roles in infection, autoimmunity, vaccination, and tumor immunology.
• EV-Based Therapeutics and Diagnostics in Immunology: Applications in immune modulation, immunotherapy, and biomarker discovery.
• Technological Innovations: Advances in isolation, functional assays, and imaging to dissect EV-immune interactions.

Submissions should emphasize novel immunological insights, mechanisms, or translational applications that advance understanding of EV biology within the immune system.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Extracellular Vesicles, Immune Regulation, Cytokine Networks, Antigen Presentation, Host–Microbiome Interactions, Autoimmunity, Immunotherapy, Infection

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.