Document Type : Original Article
Authors
Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Abstract
Background: T-helper 17 (Th17) cell response is engaged in the onset of allergic rhinitis (AR). Moreover, interleukin (IL)-38 is thought to be involved in inhibiting cytokine secretion in the Th17 pathway.
Objective: To evaluate the regulatory function of IL-38 on abnormal Th17 responses in Chinese patients with AR.
Methods: Forty-five participants, divided into an AR group (n=25) and a control group (n=20), were recruited for the study. In addition, the expression of IL-38 and Th17-related cytokines was measured as well as the Th17 cell count in participants. By implementing recombinant IL-38 (rIL-38), the intervention of human peripheral blood mononuclear cells (PBMCs) was performed. Then, flow cytometry, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used to detect theTh17 milieu.
Results: The expression of IL-38 in the AR group notably reduced compared with that in the control, whereas Th17 cell frequency and the expression levels of its transcription factor (RORC) and cytokines (IL-17A and IL-23) increased. The differentiation and immune function of Th17 cells in PBMCs were inhibited by rIL-38.
Conclusion: Th17 responses are inhibited by IL-38 in patients with AR. Therefore, the obtained findings indicate that IL-38 is a potential therapeutic target for Chinese patients with AR.
Keywords
- Papapostolou G, Kiotseridis H, Romberg K, Dahl Å, Lindgren M, Tufvesson E, et al. Cognitive dysfunction and quality of life during pollen season in children with seasonal allergic rhinitis. Pediatr Allergy Immunol. 2021;32:67–76.
- Kef K, Güven S. The prevalence of allergic rhinitis and associated risk factors among university students in Anatolia. J Asthma Allergy. 2020;13:589–97.
- Bosnic-Anticevich S, Smith P, Abramson M, Hespe CM, Johnson M, Price DB, et al. Impact of allergic rhinitis on the day-to-day lives of children: insights from an Australian cross-sectional study. BMJ Open. 2020;10:
- Kakaje A, Alhalabi MM, Alyousbashi A, Ghareeb A. Allergic rhinitis, asthma and laryngopharyngeal reflux disease: a cross-sectional study on their reciprocal relations. Sci Rep. 2021;11:2870.
- Wang J, Qiu L, Chen Y, Chen M. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis. Open Med (Wars). 2021;16:826–32.
- Li J, Lin X, Liu X, Ma Z, Li Y. Baicalin regulates Treg/Th17 cell imbalance by inhibiting autophagy in allergic rhinitis. Mol Immunol. 2020;125:162–71.
- Mantovani A, Dinarello CA, Molgora M, Garlanda C. Interleukin-1 and related cytokines in the regulation of inflammation and immunity. Immunity. 2019;50:778–95.
- Conti P, Pregliasco FE, Bellomo RG, Gallenga CE, Caraffa A, Kritas SK, et al. Mast cell cytokines IL-1, IL-33, and IL-36 mediate skin inflammation in psoriasis: a novel therapeutic approach with the anti-inflammatory cytokines IL-37, IL-38, and IL-1Ra. Int J Mol Sci. 2021;22:8076.
- Chi HH, Hua KF, Lin YC, Tsai YL, Liu FC, Chen A, et al. IL-36 signaling facilitates activation of the NLRP3 inflammasome and IL-23/IL-17 axis in renal inflammation and fibrosis. J Am Soc Nephrol. 2017;28:2022–37.
- Wang XR, Xiao JP, Wang DG. Elevated levels of serum IL-36α in patients with systemic lupus erythematosus. Biomed Rep. 2021;15:76.
- Han MM, Yuan XR, Shi X, Zhu XY, Su Y, Xiong DK, et al. The pathological mechanism and potential application of IL-38 in autoimmune diseases. Front Pharmacol. 2021;12:732790.
- Kolbinger F, Loesche C, Valentin MA, Jiang X, Pieber TR, Patel DD. β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis. J Allergy Clin Immunol. 2017;139:923–32.
- Bousquet J, Schünemann HJ, Samolinski B, Demoly P, Baena-Cagnani CE, Bachert C, et al. Allergic rhinitis and its impact on asthma (ARIA): achievements in 10 years and future needs. J Allergy Clin Immunol. 2012;130:1049–62.
- Ke X, Song S, Wang X, Shen Y, Kang H, Hong S. Associations of single nucleotide polymorphisms of PTPN22 and Ctla4 genes with the risk of allergic rhinitis in a Chinese Han population. Hum Immunol. 2017;78:227–31.
- Chen S, Guo C, Wang R, Feng Z, Liu Z, Wu L, et al. Monocytic MDSCs skew Th17 cells toward a pro-osteoclastogenic phenotype and potentiate bone erosion in rheumatoid arthritis. Rheumatology (Oxford). 2021;60:2409–20.
- Luo D, Chen Y, Zhou N, Li T, Wang H. Blockade of Th17 response by IL-38 in primary Sjögren's syndrome. Mol Immunol. 2020;127:107–11.
- Peng Z, Hu Y, Ren J, Yu N, Li Z, Xu Z. Circulating Th22 cells, as well as Th17 cells, are elevated in patients with renal cell carcinoma. Int J Med Sci. 2021;18:99–108.
- Tantilipikorn P, Siriboonkoom P, Sookrung N, Thianboonsong A, Suwanwech T, Asanasaen P, et al. Prevalence of local allergic rhinitis to Dermatophagoides pteronyssinus in chronic rhinitis with negative skin prick test. Asian Pac J Allergy Immunol. 2021;39:111–6.
- Steelant B, Seys SF, Van Gerven L, Van Woensel M, Farré R, Hellings PW, et al. Histamine and T helper cytokine-driven epithelial barrier dysfunction in allergic rhinitis. J Allergy Clin Immunol. 2018;141:951–63.
- Ouyang H, Cheng J, Du J, Gan H, Zheng L. Interleukin-27 suppresses T helper-17 inflammation in allergic rhinitis. Iran J Immunol. 2020;17:275–82.
- M, Bystrom J, Janson C. Evidence for eosinophil and IL-17 mediated inflammation in allergic rhinitis. Clin Mol Allergy. 2020;18:6.
- Wang M, Zhang W, Shang J, Yang J, Zhang L, Bachert C. Immunomodulatory effects of IL-23 and IL-17 in a mouse model of allergic rhinitis. Clin Exp Allergy. 2013; 43:956–66.
- Zhang YL, Han DH, Kim DY, Lee CH, Rhee CS. Role of interleukin-17A on the chemotactic responses to CCL7 in a murine allergic rhinitis model. PLoS One. 2017;12:e0169353.
- Zarrabi M, Nazarinia M, Rahimi Jaberi A, Gholijani N, Amirghofran Z. Elevated IL-38 serum levels in newly diagnosed multiple sclerosis and systemic sclerosis patients. Med Princ Pract. 2021;30:146–53.
- Furue K, Yamamura K, Tsuji G, Mitoma C, Uchi H, Furue M, et al. Highlighting interleukin-36 signaling in plaque psoriasis and pustular psoriasis. Acta Derm Venereol. 2018;98:5–13.
- Zarrabi M, Gholijani N, Shenavandeh S, Aflaki E, Amirghofran Z. IL-38 serum levels in patients with Behcet's disease and the relationship with clinical features. Eur Cytokine Netw. 2019;30:82–7.
- Xie C, Yan W, Quan R, Chen C, Tu L, Hou X, et al. Interleukin-38 is elevated in inflammatory bowel diseases and suppresses intestinal inflammation. Cytokine. 2020;127:154963.
- Xu WD, Su LC, Liu XY, Wang JM, Yuan ZC, Qin Z, et al. IL-38: A novel cytokine in systemic lupus erythematosus pathogenesis. J Cell Mol Med. 2020;24:12379–89.
- Xie F, Hu Q, Cai Q, Yao R, Ouyang S. IL-35 inhibited Th17 response in children with allergic rhinitis. ORL J Otorhinolaryngol Relat Spec. 2020;82:47–52.
- Li J, Lin X, Liu X, Ma Z, Li Y. Baicalin regulates Treg/Th17 cell imbalance by inhibiting autophagy in allergic rhinitis. Mol Immunol. 2020;125:162–71.
- Han Y, Mora J, Huard A, da Silva P, Wiechmann S, Putyrski M, et al. IL-38 ameliorates skin inflammation and limits IL-17 production from γδ T cells. Cell Rep. 2019;27:835–46.
- Mora J, Schlemmer A, Wittig I, Richter F, Putyrski M, Frank AC, et al. Interleukin-38 is released from apoptotic cells to limit inflammatory macrophage responses. J Mol Cell Biol. 2016;8:426–38.
- van de Veerdonk FL, Stoeckman AK, Wu G, Boeckermann AN, Azam T, Netea MG, et al. IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist. Proc Natl Acad Sci U S A. 2012;109:3001–5.
- Yuan X, Peng X, Li Y, Li M. Role of IL-38 and its related cytokines in inflammation. Mediators Inflamm. 2015;2015:807976.
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