I. Pathogenesis
 

(I) IgE-Mediated Immune Response
 

When a susceptible individual is initially exposed to an allergen (such as pollen, dust mites, animal dander, etc.), the immune system produces specific IgE antibodies. These IgE antibodies bind to high-affinity IgE receptors (FcεRI) on the surface of mast cells and basophils in the nasal mucosa, leading to a sensitized state. Upon re-exposure to the allergen, the allergen binds to IgE, activating mast cells and basophils. This triggers the release of inflammatory mediators like histamine and leukotrienes, causing the immediate-phase reaction characterized by nasal itching, sneezing, and watery discharge.
 

 

Resource：pubmed

(II) Th1/Th2 Immune Response Imbalance
 

An imbalance in the Th1/Th2 immune response is a key factor in the pathogenesis of allergic rhinitis. In allergic reactions, cytokines (such as IL-4, IL-5, IL-13) secreted by Th2 cells promote the production of IgE and the infiltration of eosinophils, thereby exacerbating the inflammatory response.
 

(III) Neuroimmune Dysregulation
 

During episodes of allergic rhinitis, levels of substance P and calcitonin gene-related peptide secreted by nerve fibers around the nasal mucosal glands are significantly elevated, which is closely related to nasal hyperresponsiveness. Type 2 T follicular helper cells and T follicular regulatory cells play regulatory roles in IgE production, while group 2 innate lymphoid cells are involved in the initiation of the type 2 immune response in early AR.

(IV) Non-IgE-Mediated Inflammatory Response
 

Certain allergens, through their enzymatic activity, can induce epithelial cells to produce cytokines and chemokines that promote a Th2 response. Alternatively, they may weaken the tightness of epithelial junctions, disrupting the epithelial barrier function and facilitating contact between dendritic cells and allergens. Although remodeling of nasal tissue in AR is less pronounced than the bronchial tissue remodeling seen in asthma, its mechanisms in AR pathogenesis are not yet fully understood.
 

Gene Therapy
 

(I) Targeted Silencing of Disease-Causing Genes
 

Utilizing nucleic acid technology to specifically inhibit the expression of key pathogenic factors:
 

Antisense oligonucleotides/RNA interference technology:   Designing specific sequences to target the mRNA of IL-4, IL-5, IL-13, or the transcription factor GATA-3, promoting their degradation and thereby blocking Th2 cytokine production and IgE class switching.
 

DNAzyme technology: Using catalytic DNA molecules to directly cleave target mRNA, efficiently inhibiting the synthesis of inflammatory mediators.
 

MicroRNA antagonists: Neutralizing pro-inflammatory miRNAs like miR-145, lifting their suppression of immunoregulatory genes, and restoring immune balance.
 

(II) Reshaping Immune Balance
 

Using viral vectors (such as AAV) to mediate the overexpression of protective genes:

Introducing Th1-stimulating factor genes: Such as IL-12 or IFN-γ, to promote Th1 differentiation and reverse the Th2 bias.
 

Enhancing immunoregulatory function:Overexpressing anti-inflammatory cytokines like IL-10 or TGF-β to actively suppress inflammation and induce immune tolerance.
 

Transgenic Mouse Models
 

IL-4 Gene-Edited Mice:   Enhanced IL-4 expression or signaling promotes IgE production by B cells, mimicking the Th2 immune-dominant state seen in human AR.
 

IL-5 Gene-Edited Mice: Exhibit increased eosinophil (EOS) infiltration and airway inflammation, modeling the pathological feature of increased EOS in the nasal mucosa of AR patients.
 

FcεRIγ -/- Mouse Model:   Lacks the γ chain of the high-affinity IgE receptor, blocking mast cell/basophil activation and thus preventing the initiation of the IgE-mediated allergic reaction.
 

DC-SIGN Knockout Mice:   Have defective dendritic cell (DC) function, revealing the role of DCs in capturing allergens and presenting them to Th2 cells.
 

TLR4 Knockout Mice: Exhibit a weakened response to endotoxins (like LPS), revealing the association between innate immune recognition and AR.
 

MingCeler Biotech's Tetraploid Complementation Technology
 

Traditional animal model technologies, including pronuclear microinjection and ES cell targeting chimera technology, follow a "mouse-making-mouse" model. This requires 2-3 generations of breeding to obtain homozygous mice, a process taking at least 6-8 months or even years. Mingxun Biotech, leveraging its self-developed TurboMice™ technology, has developed numerous disease mouse models. TurboMice™ technology overcomes the challenges of long modeling cycles and low success rates for complex models. It enables gene editing at almost any target locus and can generate complete homozygous gene-edited mouse models directly from embryonic stem cells in as short as 2 months.

MingCeler Biotech can customize various AR mouse models according to client needs, such as IL-4 gene-edited mice, IL-5 gene-edited mice, FcεRIγ -/- mouse models, DC-SIGN knockout mice, and TLR4 knockout mice. We welcome inquiries from all researchers

 

References:
 

[1] Wang X, Xiong J, Xiang J, et al. Research progress on the role of type 2 immune response in the pathogenesis of allergic rhinitis[J]. International Journal of Otolaryngology-Head and Neck Surgery, 2021, 45(4): 219-222. DOI: 10.3760/cma.j.issn.1673-4106.2021.04.009.

[2] Cai S, Lou H. [Neuroimmunomodulation in allergic rhinitis]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2021 Sep;35(9):859-864. Chinese. doi: 10.13201/j.issn.2096-7993.2021.09.021. PMID: 34628846; PMCID: PMC10127821.

[3] Baraniuk JN. Pathogenesis of allergic rhinitis. J Allergy Clin Immunol. 1997 Feb;99(2):S763-72. doi: 10.1016/s0091-6749(97)70125-8. PMID: 9042069.

[4] Sweerus K, Lachowicz-Scroggins M, Gordon E, LaFemina M, Huang X, Parikh M, Kanegai C, Fahy JV, Frank JA. Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma. J Allergy Clin Immunol. 2017 Jan;139(1):72-81.e1. doi: 10.1016/j.jaci.2016.02.035. Epub 2016 Apr 20. PMID: 27215490; PMCID: PMC5073041.

 

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