circRNA/TLR interaction: key players in immune regulation and autoimmune diseases

Circular RNAs are a class of non-coding RNAs with covalently closed loops. They have been revealed to regulate immune responses by affecting gene expression. Although initially considered splicing byproducts, new studies have indicated their role in transcriptional and post-transcriptional control, especially with TLRs. TLRs start inflammatory signaling and let the innate immune system recognize PAMPs. circRNAs interact context-dependently with TLR pathways to influence immune homeostasis and inflammation in either pathogenic or protective roles. In autoimmune diseases, dysregulated circRNA expression can aggravate immune responses and damage tissue. CircRNAs can interact with RNA-binding proteins, function as molecular sponges for miRNAs, and change inflammatory pathways like the NF-κB signaling cascade, influencing immune responses. They control adaptive immunity, function of antigen-presenting cells, and cytokine generation. The stability and presence of circRNAs in many body fluids make them therapeutic targets and biomarkers for inflammatory and autoimmune diseases. The several immune control roles of circRNA-TLR interactions are discussed in this review, as well as their consequences for immunologically mediated disease diagnosis and treatment.