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      MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases?

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          Abstract

          MicroRNAs (miRNAs) are small non-coding RNA molecules that are 18–22 nucleotides long and highly conserved throughout evolution. Currently, they are considered one of the fundamental regulatory mechanisms of genes expression. It has been demonstrated that miRNAs are involved in many biologic processes, such as signal transduction, cell proliferation and differentiation, apoptosis and stress responses. More recently, the role of miRNA has also been revealed in numerous immunological and inflammatory disorders, including allergic inflammation. Specific miRNA profiles were demonstrated in asthma, allergic rhinitis and atopic dermatitis. A core set of miRNAs involved in atopic diseases include upregulated miR-21, miR-223, miR-146a, miR-142-5p, miR-142-3p, miR-146b, miR-155 and downregulated let-7 family, miR-193b and miR-375. Most of the involved miRNAs increase secretion of Th2 cytokines (miR-1248, miR-146b), decrease secretion of Th1 cytokines (miR-513-5p, miR-625-5p) or promote differentiation of T cells towards Th2 (miR-21, miR-19a). In asthma miR-140-3p, miR-708 and miR-142-3p play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. Some single miRNAs or, more probably, their sets hold the promise for their use as biomarkers of atopic diseases. They are also promising target of future therapies.

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          Most cited references90

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          Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision.

          Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update.
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            Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I

            This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti-inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long-term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long-term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti-inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.
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              MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression.

              Allergic airway inflammation is characterized by marked in situ changes in gene and protein expression, yet the role of microRNAs (miRNAs), a new family of key mRNA regulatory molecules, in this process has not yet been reported. Using a highly sensitive microarray-based approach, we identified 21 miRNAs with differential expression between doxycycline-induced lung-specific IL-13 transgenic mice (with allergic airway inflammation) and control mice. In particular, we observed overexpression of miR-21 and underexpression of miR-1 in the induced IL-13 transgenic mice compared with control mice. These findings were validated in two independent models of allergen-induced allergic airway inflammation and in IL-4 lung transgenic mice. Although IL-13-induced miR-21 expression was IL-13Ralpha1 dependent, allergen-induced miR-21 expression was mediated mainly independent of IL-13Ralpha1 and STAT6. Notably, predictive algorithms identified potential direct miR-21 targets among IL-13-regulated lung transcripts, such as IL-12p35 mRNA, which was decreased in IL-13 transgenic mice. Introduction of pre-miR-21 dose dependently inhibited cellular expression of a reporter vector harboring the 3'-untranslated region of IL-12p35. Moreover, mutating miR-21 binding sites in IL-12p35 3'-untranslated region abrogated miR-21-mediated repression. In summary, we have identified a miRNA signature in allergic airway inflammation, which includes miR-21 that modulates IL-12, a molecule germane to Th cell polarization.
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                Author and article information

                Contributors
                specjalski@gumed.edu.pl
                Journal
                Arch Immunol Ther Exp (Warsz)
                Arch. Immunol. Ther. Exp. (Warsz.)
                Archivum Immunologiae et Therapiae Experimentalis
                Springer International Publishing (Cham )
                0004-069X
                1661-4917
                28 May 2019
                28 May 2019
                2019
                : 67
                : 4
                : 213-223
                Affiliations
                ISNI 0000 0001 0531 3426, GRID grid.11451.30, Department of Allergology, , Medical University of Gdańsk, ; Dębinki 7, 80-210 Gdańsk, Poland
                Author information
                http://orcid.org/0000-0002-1821-1266
                Article
                547
                10.1007/s00005-019-00547-4
                6597590
                31139837
                4b93c4d0-79f9-47aa-9688-3559e92b4ecf
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 12 January 2019
                : 13 May 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100010609, Gdański Uniwersytet Medyczny;
                Award ID: ST-554
                Award Recipient :
                Categories
                Review
                Custom metadata
                © L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019

                Immunology
                mirna,allergy,asthma,allergic rhinitis,atopic dermatitis
                Immunology
                mirna, allergy, asthma, allergic rhinitis, atopic dermatitis

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