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Non-coding RNAs; Immune regulation; MicroRNAs; Long non-coding RNAs; Circular RNAs; Disease pathogenesis

Introduction

The immune system plays a critical role in defending the host against pathogens and maintaining tissue homeostasis. Dysregulation of immune responses contributes to the pathogenesis of various diseases, including autoimmune disorders, cancer, infectious diseases, and inflammatory conditions [1]. Recent advances in molecular biology have uncovered the complexity of gene regulation beyond proteincoding sequences, revealing the importance of non-coding RNAs (ncRNAs) in modulating immune functions and disease processes. In this review, we provide an overview of the roles of ncRNAs in immune regulation and their implications in disease pathogenesis.

MicroRNAs (miRNAs) in Immune Regulation

MicroRNAs (miRNAs) are small non-coding RNAs approximately 19-22 nucleotides in length that post-transcriptionally regulate gene expression by binding to target mRNAs, leading to mRNA degradation or translational repression (Table 1) [2]. In the context of the immune system, miRNAs play critical roles in the regulation of immune cell development, differentiation, and function. For instance, miR-155 is involved in the activation of T cells and the polarization of macrophages towards an inflammatory phenotype. Conversely, miR-146a acts as a negative regulator of innate immune responses by targeting key signaling molecules such as IRAK1 and TRAF6.

Table 1: Examples of microRNAs (miRNAs) in Immune Regulation

Long Non-Coding RNAs (lncRNAs) in Immune Modulation

Long non-coding RNAs (lncRNAs) are a heterogeneous group of transcripts longer than 200 nucleotides that lack protein-coding capacity (Table 2) [3]. Emerging evidence suggests that lncRNAs play diverse roles in immune regulation by modulating chromatin remodeling, transcriptional regulation, and post-transcriptional processes. For example, lncRNA HOTAIR regulates the expression of inflammatory genes in macrophages by interacting with chromatinmodifying complexes. Additionally, lncRNA NEAT1 promotes the activation of the innate immune response by facilitating the formation of paraspeckles and the nuclear retention of immune-related transcripts.

Table 2: Long Non-Coding RNAs (lncRNAs) in Immune Modulation

Circular RNAs (circRNAs) in Immune Responses

Circular RNAs (circRNAs) are a class of covalently closed RNA molecules generated through back-splicing events. Although initially considered as byproducts of pre-mRNA splicing, circRNAs have emerged as important regulators of gene expression at the transcriptional and post-transcriptional levels [4,5]. In the immune system, circRNAs have been implicated in the modulation of immune cell functions, cytokine production, and inflammatory responses. For instance, circRNA circHIPK3 regulates macrophage activation and polarization by sponging miR-124 and derepressing the expression of its target genes.=

Dysregulation of ncRNAs in Disease Pathogenesis

Aberrant expression of ncRNAs has been associated with the pathogenesis of various immune-related disorders, offering potential diagnostic and prognostic biomarkers. In autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, dysregulated miRNAs and lncRNAs contribute to the dysregulation of immune responses and the perpetuation of chronic inflammation [6,7]. Similarly, altered expression of ncRNAs has been observed in cancer, infectious diseases, and inflammatory conditions, highlighting their multifaceted roles in disease pathogenesis.

Therapeutic Targeting of ncRNAs

Given their critical roles in immune regulation and disease pathogenesis, ncRNAs represent attractive therapeutic targets for the development of novel treatment strategies. Approaches such as antagomirs, antisense oligonucleotides, and small molecule inhibitors have been explored to modulate the expression and activity of specific ncRNAs for therapeutic purposes [8]. Furthermore, the development of delivery systems that enable targeted delivery of ncRNA-based therapeutics holds promise for precision medicine approaches in immune-mediated disorders.

Conclusion

Non-coding RNAs exert profound effects on immune regulation and disease pathogenesis through diverse mechanisms of action. Elucidating the functions of ncRNAs in immune cell biology and inflammatory processes provides insights into the development of diagnostic biomarkers and therapeutic interventions for immunerelated disorders. Continued research into the roles of ncRNAs in immune regulation promises to uncover novel therapeutic targets and strategies for the treatment of autoimmune diseases, cancer, infectious diseases, and other immune-mediated conditions.

References

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