Novel Modulators of Asthma and Allergy: Exosomes and MicroRNAs

Abstract

Intercellular communication is crucial to the immune system response. In the recent years, the discovery of exosomes has changed the way immune response orchestration was understood. Exosomes are able to operate as independent units that act as mediators in both physiological and pathological conditions. These structures contain proteins, lipidic mediators, and nucleic acids and notoriously include microRNAs (miRNAs). miRNAs are short RNA sequences (around 19–22 nucleotides) with a high phylogenetic conservation and can partially or totally regulate multiple mRNAs, inhibiting protein synthesis. In respiratory diseases such as asthma and allergic sensitization, exosomes released by several cell types and their specific content perform crucial functions in the development and continuation of the pathogenic mechanisms. Released exosomes and miRNAs inside them have been found in different types of clinical samples, such as bronchoalveolar lavage fluids and sputum supernatants, providing new data about the environmental factors and mediators that participate in the inflammatory responses that lead to the exacerbation of asthma. In this review, we summarize our current knowledge of the role of exosomes and miRNAs in asthma and allergic sensitization, paying attention to the functions that both exosomes and miRNAs are described to perform through the literature. We review the effect of exosomes and miRNAs in cells implicated in asthma pathology and the genes and pathways that they modify in them, depicting how their behavior is altered in disease status. We also describe their possible repercussion in asthma diagnosis through their possible role as biomarkers. Therefore, both exosomes and miRNAs can be viewed as potential tools to be added to the arsenal of therapeutics to treat this disease.

Asthma diagnosis using integrated analysis of eosinophil microRNAs

“…miRNAs differential expression is unlikely to be a mere epigenetic phenomenon of asthma as it has been demonstrated that miRNAs directly or indirectly affect the expression of multiple genes associated with inflammatory response; thus, miR‐16 downregulates TNF α; the miR‐17~92 cluster modifies PTEN ; miR‐155 alters PU.1 , c‐Maf , and SOCS1 ; and miR‐146a regulates TRAF6 and IRAK1 . Others miRNAs have been related to the pathology of asthma and allergy as miR‐21 that is upregulated in steroid‐resistant asthma targeting IL‐12p35 ; the miR‐1248 targeting IL‐5; and miR‐15a inhibiting VEGFA in CD4 + cells . Furthermore, the miRNAs that we have found differentially expressed in eosinophils from asthmatics have predicted targets that may be related to asthma physiopathology: MAPK1 , AKT1 , CDC42 , RHOA , PTEN , SMAD3 , VEGFA , TGFBR1 , and STAT3 using miRSystem (software for miRNA target determination, data not shown).…”

Exosomes: an important messenger in the asthma inflammatory microenvironment

“…Therefore, it is necessary to investigate the exosomal load and composition and whether such a process depends on the cellular origins. 41 The exosomal miRNA profile is likely to reflect, in part, the cellular composition of the BALF because exosomes are cellular secretory products. Different cellular compositions of BALF between healthy controls and patients with asthma can result in distinct exosomal miRNAs as different cells produce different exosomes.…”

Small RNA Sequencing Reveals Exosomal miRNAs Involved in the Treatment of Asthma by Scorpio and Centipede

“…Additionally, miRNAs have also been shown to function as potential biomarkers and therapeutic target for asthma [12]. e biological roles of exosomal miRNAs have attracted significant interest in the pulmonary field [13,14]. Exosomal miRNAs from the BALF, such as let-7 and miRNA-200, can act as novel biomarkers for asthmatic patients [15].…”