Suppression of  Il5  and  Il13  Gene Expression by Synthetic siRNA Molecules Reduces Nasal Hyperreactivity and Inflammation in a Mouse Model of Allergic Rhinitis

M. M. Kaganova; Каганова М. М.; I. P. Shilovsky; Шиловский И. П.; V. I. Kovchina; Ковчина В. И.; E. D. Timotievich; Тимотиевич Е. Д.; T. E. Rusak; Русак Т. Е.; A. A. Nikolsky; Никольский А. А.; K. V. Yumashev; Юмашев К. В.; G. B. Pasikhov; Пасихов Г. Б.; K. V. Vinogradova; Виноградова К. В.; D. A. Gursky; Гурский Д. А.; M. V. Popova; Попова М. В.; V. E. Brylina; Брылина В. Е.; M. R. Khaitov; Хаитов М. Р.

doi:10.31857/S0320972525040039

Suppression of Il5 and Il13 Gene Expression by Synthetic siRNA Molecules Reduces Nasal Hyperreactivity and Inflammation in a Mouse Model of Allergic Rhinitis

作者: Kaganova M.M.¹, Shilovsky I.P.¹, Kovchina V.I.¹, Timotievich E.D.¹, Rusak T.E.¹, Nikolsky A.A.¹, Yumashev K.V.¹, Pasikhov G.B.¹, Vinogradova K.V.¹^,2, Gursky D.A.¹^,2, Popova M.V.¹^,3, Brylina V.E.², Khaitov M.R.¹^,3
隶属关系:
1. Institute of Immunology National Research Center
2. Moscow State Academy of Veterinary Medicine and Biotechnology – Skryabin MVA
3. Pirogov Russian National Research Medical University
期: 卷 90, 编号 4 (2025)
页面: 531-549
栏目: Articles
URL: https://rjeid.com/0320-9725/article/view/685803
DOI: https://doi.org/10.31857/S0320972525040039
EDN: https://elibrary.ru/IHUKFB
ID: 685803

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Th2 cytokines (IL-4, IL-5, and IL-13) play an important role in the development of allergies, including allergic rhinitis (AR). IL-13 promotes mucus hypersecretion in the airways and IL-5 recruits eosinophils to the nasal mucosa, leading to increased inflammation and tissue damage. Drugs based on monoclonal antibodies that block the activity of these cytokines are being developed for the treatment of allergic diseases. However, studies of drugs that target IL-13 alone (such as Tralokinumab and Lebrikizumab) were not successful. Given that IL-5 and IL-13 have different roles in AR, simultaneous inhibition of both cytokines may be a promising approach. New methods of regulating gene activity, such as RNA interference (RNAi), offer new perspectives for the development of drugs. This study describes a complex consisting of siRNAs that inhibit the activity of Il5 or Il13 genes and a currier peptide LTP. The effects of this complex on the allergic inflammation in a mouse model of AR was studied. Suppression of Il5 expression decreased nasal hyperreactivity and reduced the number of goblet cells in the respiratory epithelium of AR-induced mice. Inhibiting the Il13 gene had a more beneficial effect than suppression Il5 alone, further contributing to reducing the number of cells infiltration the nasal cavity. When both Il5 and Il13 were suppressed simultaneously, the result was similar to that of Il13 inhibition alone. Likely, IL-13 plays a more significant role in the development of AR than IL-5. As a result, the possibility of using RNAi for anti-cytokine therapy for AR has been demonstrated. However, dual inactivation of IL-5 and IL-13 by siRNAs does not provide any advantages over inactivating IL-13 alone in the current mouse model of AR. However, the lack of success of anti-IL-13 therapy in clinical practice indicates the promise of an approach based on the dual blocking of IL-5 and IL-13.

关键词

allergy, cytokines, RNA interference, IL-5, IL-13, Th2 immune response