집먼지진드기로 유발한 알레르기비염 면역치료 모델의 개발
Development of a house dust mite-induced mouse model for allergen-specific immunotherapy in allergic rhinitis
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: Allergen-specific immunotherapy (AIT) is the only known curative treatment for allergic diseases. Recently, novel immunotherapies have been developed to overcome the inconvenience and adverse reactions associated with conventional AIT. Validated animal models are essential for screening novel immunotherapies; however, effective models for AIT in allergic rhinitis (AR) are lacking. Herein, we aimed to develop an optimal protocol for AIT using a house dust mite (HDM)-induced AR mouse model. Methods: BALB/c mice were intraperitoneally injected with the alum-absorbed HDM extract (5 μg) on days 0, 7, and 14. Sensitized mice were administered three subcutaneous injections of HDM extract (250 μg/100 μL; SCIT group) and phosphate-buffered saline (100 μL; negative and positive control groups) at 2-day intervals. Next, HDM extract (25 μg) was intranasally administered to SCIT and positive control groups for five consecutive days. Nasal symptoms, ear swelling, eosinophil count, antibody levels, and nasal mucosa histopathology were assessed in all groups. Cytokine production was analyzed in the splenocyte culture supernatant. Results: Compared with the positive control group, the SCIT group exhibited reduced nasal symptoms, ear swelling, and eosinophil count in nasopharyngeal lavage. Compared with the positive control group, the SCIT group had reduced eosinophil, mast cell, and goblet cell counts in the nasal mucosa. Serum levels of HDM-specific IgG1 were higher in the SCIT group than in the positive control group. The stimulation index of splenocytes was reduced in the SCIT group when compared with that in the positive control group. Compared with the positive control group, the SCIT group exhibited decreased levels of interleukin (IL)-4 and IL-17, whereas those of IL-10 and interferon-gamma levels were increased. Conclusion: AR mice treated with the AIT-HDM protocol showed attenuated nasal symptoms and improved histopathological findings and cytokine profiles compared with the untreated AR mice. Our findings suggest that the examined model may be useful for screening new AITs.
Abstract
Purpose: Allergen-specific immunotherapy (AIT) is the only known curative treatment for allergic diseases. Recently, novel immunotherapies have been developed to overcome the inconvenience and adverse reactions associated with conventional AIT. Validated animal models are essential for screening novel immunotherapies; however, effective models for AIT in allergic rhinitis (AR) are lacking. Herein, we aimed to develop an optimal protocol for AIT using a house dust mite (HDM)-induced AR mouse model. Methods: BALB/c mice were intraperitoneally injected with the alum-absorbed HDM extract (5 μg) on days 0, 7, and 14. Sensitized mice were administered three subcutaneous injections of HDM extract (250 μg/100 μL; SCIT group) and phosphate-buffered saline (100 μL; negative and positive control groups) at 2-day intervals. Next, HDM extract (25 μg) was intranasally administered to SCIT and positive control groups for five consecutive days. Nasal symptoms, ear swelling, eosinophil count, antibody levels, and nasal mucosa histopathology were assessed in all groups. Cytokine production was analyzed in the splenocyte culture supernatant. Results: Compared with the positive control group, the SCIT group exhibited reduced nasal symptoms, ear swelling, and eosinophil count in nasopharyngeal lavage. Compared with the positive control group, the SCIT group had reduced eosinophil, mast cell, and goblet cell counts in the nasal mucosa. Serum levels of HDM-specific IgG1 were higher in the SCIT group than in the positive control group. The stimulation index of splenocytes was reduced in the SCIT group when compared with that in the positive control group. Compared with the positive control group, the SCIT group exhibited decreased levels of interleukin (IL)-4 and IL-17, whereas those of IL-10 and interferon-gamma levels were increased. Conclusion: AR mice treated with the AIT-HDM protocol showed attenuated nasal symptoms and improved histopathological findings and cytokine profiles compared with the untreated AR mice. Our findings suggest that the examined model may be useful for screening new AITs.
참고문헌 (24)
- 강성윤, "임파선내항원특이면역요법", Allergy Asthma & Respiratory Disease, 8(2), pp.53~65 (2020), 대한 소아알레르기 호흡기학회[DOI]
- 강성윤, "알레르기성 호흡기 질환에서의 항원특이면역요법", 대한내과학회지, 95(6), pp.370~376 (2020), 대한내과학회[DOI]
- Byeong-Gon Kim, "Combined Effects of Lactobacillus rhamnosus and Egg Oral Immunotherapy in a Mouse Model of Egg Allergy", Allergy, Asthma & Immunology Research, 12(4), pp.701~711 (2020), 대한천식알레르기학회
- Brimnes J, "Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis", Clin Exp Allergy, 37, pp.488~497 (2007)
- Xi GP, "Establishment and characterization of murine models of asthma and subcutaneous immunotherapy for Humulus pollen allergy", Immun Inflamm Dis, 9, pp.443~455 (2021)
- Hesse L, "Methods for experimental allergen immunotherapy : subcutaneous and sublingual desensitization in mouse models of allergic asthma", Methods Mol Biol, 2223, pp.295~335 (2021)
- Yasuda Y, "Group 2 innate lymphoid cells and the house dust mite-induced asthma mouse model", Cells, 9, pp.1178~ (2020)
- Hesse L, "Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model", Allergy, 73, pp.862~874 (2018)
- Hesse L, "Subcutaneous immunotherapy using modified Phl p5a-derived peptides efficiently alleviates allergic asthma in mice", Allergy, 74, pp.2495~2498 (2019)
- Smarr CB, "Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre-and postsensitization", Proc Natl Acad Sci U S A, 113, pp.5059~5064 (2016)
- Joshi VB, "Biodegradable particles as vaccine delivery systems : size matters", AAPS J, 15, pp.85~94 (2013)
- Bousquet J, "ARIA-EAACI care pathways for allergen immunotherapy in respiratory allergy", Clin Transl Allergy, 11, pp.e12014~ (2021)
- Cao H, "Clinical significance of dust mite allergens", Mol Biol Rep, 47, pp.6239~6246 (2020)
- Fujita H, "Mechanisms of allergen-specific immunotherapy", Clin Transl Allergy, 2, pp.2~ (2012)
- Drazdauskaitė G, "Mechanisms of allergen immunotherapy in allergic rhinitis", Curr Allergy Asthma Rep, 21, pp.2~ (2020)
- Gonzalez M, "Dermatophagoides pteronyssinus immunotherapy changes the T-regulatory cell activity", Sci Rep, 7, pp.11949~ (2017)
- Scadding GW, "Effect of 2 years of treatment with sublingual grass pollen immunotherapy on nasal response to allergen challenge at 3 years among patients with moderate to severe seasonal allergic rhinitis : the GRASS randomized clinical trial", JAMA, 317, pp.615~625 (2017)
- Yao Y, "CD23 expression on switched memory B cells bridges T-B cell interaction in allergic rhinitis", Allergy, 75, pp.2599~2612 (2020)
- Beutier H, "IgG subclasses determine pathways of anaphylaxis in mice", J Allergy Clin Immunol, 139, pp.269~280 (2017)
- Bruhns P, "Properties of mouse and human IgG receptors and their contribution to disease models", Blood, 119, pp.5640~5649 (2012)
- Wachholz PA, "Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1 : Th2 cytokine ratios", Immunology, 105, pp.56~62 (2002)
- Amin K, "Evidence for eosinophil and IL-17 mediated inflammation in allergic rhinitis", Clin Mol Allergy, 18, pp.6~ (2020)
- Milovanovic M, "Interleukin-17A promotes IgE production in human B cells", J Invest Dermatol, 130, pp.2621~2628 (2010)
- Morita H, "Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid", J Allergy Clin Immunol, 143, pp.2190~2201 (2019)