---
title: "MicroRNAs in Immune-Related Diseases: Mechanisms, Functions and Therapeutic Perspectives"
id: "frontiers-in-immunology-14-micrornas-in-immune-related-diseases-mechanism-functions-and-therapeutic"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-14-micrornas-in-immune-related-diseases-mechanism-functions-and-therapeutic"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1943071"
published_at: "2026-09-04T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# MicroRNAs in Immune-Related Diseases: Mechanisms, Functions and Therapeutic Perspectives
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- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1943071)
- **Published At:** 2026-09-04T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source is a REVIEW article titled “MicroRNAs in immune-related diseases: mechanism, functions and therapeutic perspectives” published in Frontiers in Immunology. - The publicly available page captured by the source contains site navigation, journal information and section listings but does not include the article body, abstract, methods, results, or conclusions. - The Frontiers in Immunology journal page lists multiple topical sections (for example **Viral Immunology**, **Inflammation**, **T Cell Biology**, **Autoimmune Disorders**, **Vaccines and Molecular Therapeutics**) that are relevant to immunology research and may be pertinent to the review’s scope. - The captured content confirms the article type is a REVIEW but provides no clinical details, mechanistic descriptions, specific microRNA names, disease examples, experimental data, or therapeutic recommendations. - Because the source extract lacks the article text, specific claims about **microRNAs**, their mechanisms, functional roles, biomarker value, or therapeutic strategies are not reported and cannot be summarized or paraphrased from this source. - Readers seeking the full review should consult the original Frontiers in Immunology article page; the source record includes links and site navigation but not the manuscript content itself.
## Clinical Analysis & Structured Key Points
Frontiers | MicroRNAs in immune-related diseases: mechanism, functions and therapeutic perspectives REVIEW article Front. Immunol. , 04 September 2026 Sec. Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1943071 Published in Frontiers in Immunology Autoimmune Disorders 7 impact factor 11.3 citescore Part of a Research Topic Non-Invasive Immune Biomarkers: Liquid Biopsy for Immune-Mediated Disorders and Cancer Monitoring Submission open 9496 views 7 articles Editor & Reviewers Edited by H R Hayet RAFA Reviewed by S B Sarra BENKHELIFA I R IBTISSEM RAHIM Outline Figures and Tables Figure 1 View in article Figure 2 View in article Table 1 miRNAs play a regulatory role in the development of immune-related diseases. View in article Table 2 miRNAs are potential biomarkers for immune-related diseases. View in article REVIEW article Front. Immunol. , 04 September 2026 Sec. Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1943071 MicroRNAs in immune-related diseases: mechanism, functions and therapeutic perspectives T T Tutku Tunç 1 * S Y Serap Yaman Ozer 2 S M Sema Misir 3 1. Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Sivas Cumhuriyet University, Sivas, Türkiye 2. Department of Medical Biochemistry, Faculty of Medicine, Trabzon Kanuni Training and Research Hospital, Trabzon University, Trabzon, Türkiye 3. Department of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, Sivas, Türkiye See more Article metrics View details Abstract MicroRNAs (miRNAs) are evolutionarily conserved, non-coding RNA molecules approximately 18–25 nucleotides in length that regulate gene expression at the post-transcriptional level. Their principal mechanism of action is post-transcriptional gene silencing via RNA interference, achieved by binding to complementary sequences within target messenger RNAs (mRNAs). Accumulating evidence has highlighted the pivotal role of miRNAs in the development, differentiation, and function of immune cells, as well as in maintaining immune homeostasis. A more comprehensive understanding of the complex molecular networks governed by these miRNAs may provide valuable insights into disease mechanisms, facilitate clinical decision-making, and ultimately improve patient outcomes. The remarkable stability of miRNAs, together with their presence in the systemic circulation encapsulated within extracellular vesicles, has attracted considerable interest in their clinical application. These characteristics make circulating miRNAs promising candidates as diagnostic biomarkers for the early detection of disease and as prognostic indicators for disease progression and evaluating therapeutic efficacy. Furthermore, an increasing number of miRNA-based studies across diverse immune-related disorders have revealed their potential as therapeutic targets. The integration of synergistic therapeutic strategies and complementary miRNA-based approaches may further enhance treatment efficacy and contribute to the development of novel precision-medicine interventions for immune-related diseases. In this review, we comprehensively discuss the biogenesis and biological functions of miRNAs and examine their regulatory roles in the pathogenesis of rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis, systemic lupus erythematosus (SLE), and atopic dermatitis (AD). We are also evaluating the potential of these miRNAs as diagnostic and prognostic biomarkers, and their promising properties as therapeutic targets in the treatment of immune system-related diseases. These selected diseases represent key immune disorders in which miRNAs serve as strong biomarker candidates for early diagnosis (diagnostic) and disease course (prognostic) due to their stability in systemic circulation and their presence within extracellular vesicles. These six diseases constitute the cluster of “immune-related disorders,” where miRNA-based studies are steadily increasing, and these molecules hold the highest potential as novel therapeutic targets. 1 Introduction The immune system is a highly sophisticated and tightly regulated biological network that protects the host against invading pathogens while preserving self-tolerance and tissue homeostasis. This intricate balance relies on coordinated interactions among innate and adaptive immune cells, soluble mediators, signaling molecules, and transcriptional regulators. Under physiological conditions, immune activation is rapidly initiated upon pathogen recognition and subsequently terminated through multiple regulatory mechanisms to prevent excessive inflammation and autoimmune tissue damage ( 1 ). Dysregulation of these finely orchestrated processes contributes to the initiation and progression of a wide spectrum of immune-mediated disorders, including autoimmune diseases, chronic inflammatory conditions, allergic diseases, infectious diseases, and cancer. Consequently, elucidating the molecular mechanisms governing immune homeostasis has become one of the major objectives of modern immunology ( 2 , 3 ). Although autoimmune, autoinflammatory, allergic, and chronic inflammatory diseases differ considerably in their clinical manifestations and affected organs; they share several common molecular mechanisms, including impaired immune tolerance, persistent activation of innate and adaptive immune responses, dysregulated cytokine production, and chronic inflammation. Increasing evidence indicates that these shared mechanisms are coordinated by complex post-transcriptional regulatory networks, among which microRNAs have emerged as central modulators of immune homeostasis. Among the regulatory mechanisms controlling immune responses, epigenetic regulation has emerged as a fundamental determinant of immune cell development and function. Unlike genetic alterations, epigenetic modifications dynamically regulate gene expression without changing the underlying DNA sequence, allowing immune cells to rapidly adapt to environmental cues and inflammatory stimuli ( 4 ). DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs collectively constitute the major epigenetic mechanisms that control immune cell differentiation, activation, and maintenance of immune tolerance. Increasing evidence suggests that disruption of these epigenetic regulatory networks contributes directly to chronic inflammation, autoimmunity, and immune dysfunction, highlighting their importance in both physiological and pathological immune responses ( 4 , 5 ). Among epigenetic regulators, microRNAs (miRNAs) have attracted considerable attention for their ability to simultaneously regulate multiple genes involved in immune signaling pathways. miRNAs are evolutionarily conserved endogenous non-coding RNAs approximately 18–25 nucleotides in length that negatively regulate gene expression at the post-transcriptional level ( 6 ). By binding predominantly to complementary sequences located within the 3′ untranslated region (3′UTR) of target messenger RNAs (mRNAs), mature miRNAs induce translational repression and/or mRNA degradation, thereby fine-tuning protein synthesis. Unlike classical transcription factors that generally regulate a limited number of downstream genes, a single miRNA can modulate hundreds of target transcripts. In contrast, individual mRNAs may be simultaneously regulated by multiple miRNAs. Consequently, miRNAs function as master regulators of complex gene regulatory networks rather than simple on/off molecular switches ( 6 , 7 ). Compared with conventional protein biomarkers and individual cytokines, miRNAs possess several unique biological advantages, including remarkable molecular stability, tissue-specific expression patterns, evolutionary conservation, and the capacity to simultaneously regulate multiple signaling pathways. These characteristics make miRNAs particularly attractive candidates for both mechanistic studies and clinical applications. The immune system represents one of the biological systems most extensively controlled by miRNAs. Appropriate immune responses require precise temporal and spatial regulation of immune cell differentiation, lineage commitment, activation thresholds, cytokine production, and the resolution of inflammation ( 8 ). Many miRNAs have been identified as indispensable regulators of hematopoiesis and immune cell maturation, influencing the development and functional specialization of macrophages, dendritic cells, neutrophils, natural killer (NK) cells, B lymphocytes, CD4 + helper T cells, CD8 + cytotoxic T cells, and regulatory T cells (Tregs). Furthermore, miRNAs participate in antigen presentation, immune checkpoint regulation, inflammasome activation, pattern-recognition receptor signaling, and cytokine-mediated intercellular communication. These regulatory effects establish miRNAs as critical molecular checkpoints that prevent excessive immune activation while ensuring effective host defense ( 8 , 9 ) ( Figure 1 ). Figure 1 The role of miRNAs in immune regulation. Created with BioRender.com . Accumulating evidence demonstrates that aberrant miRNA expression is closely associated with immune-mediated diseases. Altered miRNA signatures have been identified in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), inflammatory bowel disease (IBD), psoriasis, atopic dermatitis (AD), systemic sclerosis, and many other chronic inflammatory disorders ( 10 ). Disease-associated miRNAs regulate multiple pathogenic mechanisms, including macrophage polarization, Th1/Th2/Th17 differentiation, Treg dysfunction, B-cell activation, autoantibody production, cytokine storms, oxidative stress, fibrosis, and endothelial dysfunction ( 10 – 12 ). Although many reviews have discussed the role of miRNAs in individual autoimmune or inflammatory disorders, a comprehensive comparison integrating immune regulation, disease-specific mechanisms, biomarker development, and therapeutic applications across major immune-mediated diseases is limited. Therefore, this review aims to bridge these areas by providing an integrated perspective that connects fundamental miRNA biology with emerging clinical applications. In this review, we provide a comprehensive overview of the current understanding of miRNA biology with particular emphasis on their biogenesis, molecular mechanisms of action, and regulatory roles in both innate and adaptive immunity. We further summarize recent evidence regarding the involvement of miRNAs in major immune-related diseases, discuss their emerging utility as diagnostic and prognostic biomarkers, and highlight current advances in miRNA-based therapeutic strategies. Finally, we address the major challenges and future perspectives for translating miRNA research into clinical immunology and precision medicine. 2 General overview of miRNA biology 2.1 Historical perspective and biological significance of miRNAs The discovery of miRNAs fundamentally transformed our understanding of gene regulation by revealing that protein-coding genes are not the sole determinants of cellular phenotype and biological complexity. For decades, the central dogma of molecular biology emphasized that genetic information flows from DNA to RNA and subsequently to proteins, suggesting that proteins were the principal functional molecules responsible for cellular activities. However, the identification of small non-coding regulatory RNAs demonstrated that RNA molecules themselves possess extensive regulatory functions independent of protein synthesis. This paradigm shift established non-coding RNAs as critical regulators of gene expression and initiated an entirely new era in molecular biology, developmental genetics, and systems immunology ( 13 ). The remarkable biological versatility of miRNAs has also generated considerable interest in their translational applications. Because miRNA expression changes dynamically during disease initiation and progression, disease-specific miRNA signatures have been identified in autoimmune disorders, infectious diseases, cardiovascular diseases, neurodegenerative disorders, metabolic diseases, and virtually every major cancer type. Furthermore, the exceptional stability of circulating miRNAs in serum, plasma, urine, saliva, and other body fluids has established these molecules as promising, minimally invasive biomarkers for diagnosis, prognosis, monitoring of therapeutic response, and precision medicine. Simultaneously, advances in RNA therapeutics have enabled the development of miRNA mimics and antisense oligonucleotides (antagomiRs), several of which have already entered clinical trials, highlighting the growing therapeutic potential of miRNA-based interventions ( 14 – 16 ). 2.2 miRNA biogenesis and functions miRNAs are generated through a highly coordinated and evolutionarily conserved multistep maturation process that ensures precise temporal and spatial regulation of gene expression. Unlike messenger RNAs, which function as templates for protein synthesis, miRNAs exert their biological activities by guiding post-transcriptional repression of target transcripts. Consequently, the efficiency of miRNA biogenesis directly determines the magnitude and specificity of gene silencing, making every step of the maturation pathway subject to strict molecular regulation. Increasing evidence indicates that disturbances occurring during miRNA biogenesis contribute not only to abnormal gene expression but also to immune dysregulation, chronic inflammation, tumorigenesis, and numerous human diseases. Therefore, understanding the molecular mechanisms governing miRNA biogenesis provides the essential framework for interpreting both physiological and pathological functions of miRNAs ( 17 ). The canonical miRNA biogenesis pathway begins in the nucleus, where miRNA genes are primarily transcribed by RNA polymerase II (RNA Pol II). However, a subset of miRNAs is transcribed by RNA polymerase III, depending on their genomic organization. Similar to protein-coding genes, RNA Pol II-derived primary miRNA transcripts (pri-miRNAs) undergo co-transcriptional 5′ capping with 7-methylguanosine and 3′ polyadenylation, indicating that miRNA genes share many regulatory features with conventional transcriptional units. Pri-miRNAs vary considerably in length, ranging from several hundred nucleotides to more than ten kilobases, and may contain one or multiple imperfect stem-loop structures. These transcripts can originate from independent intergenic loci, introns of protein-coding genes, exons of non-coding genes, or polycistronic miRNA clusters, thereby allowing coordinated expression of multiple functionally related miRNAs from a single transcriptional unit. This genomic diversity contributes significantly to the complexity of miRNA-mediated regulatory networks ( 17 , 18 ). Following transcription, pri-miRNAs undergo the first maturation step through the action of the Microprocessor complex, one of the most sophisticated RNA-processing machineries identified in eukaryotic cells. This nuclear complex consists principally of the RNase III endonuclease Drosha and its essential RNA-binding partner DGCR8 (DiGeorge syndrome critical region gene 8). Drosha serves as the catalytic component responsible for RNA cleavage, whereas DGCR8 functions as a molecular sensor that recognizes the characteristic stem-loop architecture of pri-miRNAs and accurately positions Drosha at the cleavage site. Structural studies have demonstrated that DGCR8 recognizes the junction between double-stranded stem regions and adjacent single-stranded RNA segments, thereby enabling highly precise processing of thousands of distinct pri-miRNA transcripts despite their considerable sequence variability ( 19 ). Drosha-mediated cleavage occurs approximately 11 base pairs from the basal junction of the hairpin structure, generating an approximately 60-70-nucleotide precursor miRNA (pre-miRNA) with the characteristic two-nucleotide 3′ overhang recognized by downstream transport machinery. This processing step is among the most tightly regulated events in the miRNA biogenesis pathway, as even minor alterations in Drosha cleavage accuracy can shift the mature miRNA sequence, particularly within its seed region (nucleotides 2–8), thereby profoundly altering target specificity ( 20 ). After nuclear processing, precursor miRNAs are actively transported to the cytoplasm through the Exportin-5/Ran-GTP transport system. Once the complex reaches the cytoplasm, hydrolysis of Ran-bound GTP induces conformational changes that release pre-miRNAs for subsequent maturation ( 19 ). Within the cytoplasm, pre-miRNAs undergo the second major processing step catalyzed by Dicer, another RNase III family endonuclease. Dicer cooperates with accessory proteins, particularly the transactivation response RNA-binding protein (TRBP) and protein activator of PKR (PACT), to precisely remove the terminal loop of the precursor hairpin. This cleavage generates an approximately 22-nucleotide miRNA duplex consisting of a guide strand and a complementary passenger strand. The interaction between Dicer and TRBP also facilitates the subsequent loading of the mature guide strand into the RNA-induced silencing complex (RISC), thereby coupling miRNA maturation directly to functional activation. Unlike the canonical miRNA biogenesis pathway, non-canonical pathways allow miRNAs to be produced via alternative cellular mechanisms without requiring either Drosha or Dicer. In these alternative processes, mirnads, rather than being cleaved by Drosha in the nucleus, are directly converted into pre-miRNA-like structures via mRNA splicing, thereby participating in biogenesis. In another important mechanism, the Dicer-independent pathway, precursor molecules transported to the cytoplasm are not cleaved by Dicer but are directly processed by the Argonaute 2 (Ago2) protein to mature into miRNAs. These non-canonical pathways enable immune cells to mount more flexible and rapid molecular responses to environmental stimuli and pathological signals, thereby expanding the regulatory capacity of miRNAs in immune homeostasis and disease pathogenesis ( 19 , 20 ) ( Figure 2 ). Figure 2 miRNA biogenesis and the miRNA-mRNA interaction mechanism. Primarily, mRNA degradation or decreased translational efficiency. Created with BioRender.com . Importantly, several regulatory checkpoints influence miRNA maturation. Mutations or altered expression of Drosha, DGCR8, Dicer, Exportin-5, or Argonaute proteins have been associated with immune dysregulation, chronic inflammation, and autoimmune diseases, emphasizing that abnormalities in miRNA biogenesis may contribute directly to disease pathogenesis rather than simply altering miRNA abundance. 3 miRNAs in immune-related diseases miRNAs have been shown to exhibit highly specific expression patterns in immune-associated organs, suggesting they play roles in the development, maturation, activation, proliferation, function, and survival of various immune cells. It is well known that dysregulated miRNA expression can lead to impaired immune tolerance and the development of immune-related diseases. With the increasing recognition that miRNAs play critical roles in regulating immune responses and immune cell development, current research has focused on the relationship between miRNAs and immune-related diseases ( 21 ). As shown in Table 1 , miRNAs play a regulatory role in the development of immune-related diseases. For example, the simultaneous increase in molecules such as miR-155 and miR-223 across multiple diseases suggests that they are central regulators of general immune activation and inflammation rather than of specific diseases. Therefore, for miRNA-based findings to become reliable diagnostic tools, it is necessary to identify disease-specific “miRNA signatures” rather than individual molecules and to integrate these
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