Unpacking EV-Cytokine Networks: Insights into Immune Regulation and Disease Dynamics

Cytokines play a central role in regulating physiological processes, largely because of their ability to orchestrate intercellular communication. As soluble signaling mediators, they bind to cell surface receptors and activate downstream pathways that can influence immune responses and subsequently lead to disease onset and/or progression. Extracellular vesicles (EVs) are heterogeneous, phospholipid membrane-bound structures- broadly sub-categorized into exosomes (endosomal origin) and ectosomes (shed formed from the plasma membrane) have emerged as important carrier of cytokines. Growing evidence shows that key cytokines, such as interleukins and tumor necrosis factor (TNF)-α, are frequently packaged within EVs. The specific cargo loaded into EVs is shaped by the physiological state and identity of the parent cell, and this cargo can profoundly influence how recipient cells are reprogrammed, particularly during disease. Despite increasing recognition of EV‑associated cytokines, their immunological significance as biomarkers of disease onset and progression remains poorly understood and warrants further investigation.This Special Feature Issue aims to advance understanding of the emerging role of extracellular vesicle (EV)–derived cytokines as modulators of immune activity and as early indicators of disease onset and progression. While cytokines are well‑established regulators of immune communication, their selective packaging within EVs adds a layer of biological complexity that remains insufficiently explored. By showcasing investigations centered on EV‑associated cytokine cargo, this collection seeks to illuminate the immunological pathways activated by these vesicle‑bound mediators and to identify the immune cell populations they influence across diverse physiological and pathological settings.Contributions to this issue will deepen insight into how EV‑derived cytokines shape immune responses, alter disease trajectories, and contribute to the development or worsening of pathological conditions. The collection further aims to broaden the conceptual framework of EV cytokine biology by examining how their molecular signatures may serve as robust biomarkers of early disease states or indicators of disease progression.In parallel, this Special Feature Issue welcomes studies evaluating whether selectively targeting EV‑associated cytokines might offer new therapeutic opportunities. Collectively, these works will position EV‑derived cytokines at the forefront of biomarker discovery and immunomodulatory research, paving the way for innovative diagnostic and treatment strategies.We welcome the submission of Original Research, Review, Mini Review, and Perspective articles on themes including, but not limited to:• EV-derived cytokines in disease onset, including studies across all physiologically relevant disease models• State-of-the-art investigations examining immunological responses triggered by EV associated cytokines, with emphasis on identifying the immune cell types involved.• Molecular and mechanistic insights into signaling cascades activated by EV derived cytokines and their roles in shaping immune function.• Therapeutic strategies targeting EV associated cytokines to modulate immune responses or ameliorate disease conditions Topic editors: Gurudutt Pendyala, Krishna M Boini, Sai S Koka Source: https://www.frontiersin.org/research-topics/76707/unpacking-ev-cytokine-networks-insights-into-immune-regulation-and-disease-dynamics