Allergic rhinitis (AR), also known as hay fever, is a common chronic inflammatory disease of the upper respiratory tract characterized by typical symptoms including rhinorrhea, nasal congestion, nasal itching, and recurrent sneezing. It is estimated that over 500 million people worldwide are affected by allergic rhinitis. In China, the prevalence of allergic rhinitis in adults reaches 17.6%, and this number has increased significantly over the past six years.
 

I. Pathogenesis
 

(I) IgE-Mediated Immune Response
 

When a sensitized individual is first exposed to allergens (such as pollen, dust mites, or animal dander), 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, establishing a sensitized state. Upon re-exposure to the allergen, the allergen binds to IgE, activating mast cells and basophils to release inflammatory mediators such as histamine and leukotrienes, triggering immediate-phase reactions including nasal itching, sneezing, and watery rhinorrhea.

 

Image source: PubMed
 

(II) Th1/Th2 Immune Response Imbalance
 

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

(III) Neuroimmune Dysregulation
 

During allergic rhinitis attacks, the levels of substance P and calcitonin gene-related peptide secreted by nerve fibers around nasal mucosal glands are significantly elevated, closely associated with nasal hyperreactivity. Type 2 follicular helper T cells and follicular regulatory T cells play regulatory roles in IgE production, while type 2 innate lymphoid cells participate in the formation of early type 2 immune responses in AR.
 

(IV) Non-IgE-Mediated Inflammatory Response
 

Certain allergens induce epithelial cells to produce cytokines and chemokines through their enzymatic activity, promoting Th2 responses. They may also weaken tight junctions and disrupt epithelial barrier function, facilitating dendritic cell contact with allergens. Although nasal tissue remodeling in AR is milder than bronchial tissue remodeling in asthma, its mechanisms in AR pathogenesis are not fully understood.
 

Gene Therapy
 

(I) Targeted Silencing of Pathogenic Genes

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

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

● DNAzyme technology: Utilizing catalytic DNA molecules to directly cleave target mRNAs, efficiently inhibiting the synthesis of inflammatory mediators.

● MicroRNA antagonists: Neutralizing pro-inflammatory miRNAs such as miR-145, relieving their inhibition of immune regulatory 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, promoting Th1 differentiation and reversing Th2 bias.

● Enhancing immune regulatory function: Overexpressing anti-inflammatory cytokines such as IL-10 or TGF-β, actively suppressing inflammation and inducing immune tolerance.
 

Mouse Models
 

IL-4 gene-edited mice: Enhanced IL-4 expression or signaling pathway promotes B cell IgE production, mimicking the Th2 immune dominance state in human AR.

IL-5 gene-edited mice: Characterized by increased eosinophil (EOS) infiltration and airway inflammation, simulating the pathological feature of increased nasal mucosal EOS in AR patients.

FcεRIγ -/- mouse model: Lacking the γ chain of the high-affinity IgE receptor, blocking mast cell/basophil activation, thereby preventing IgE-mediated allergic reactions.

DC-SIGN knockout mice: Dendritic cell (DC) functional deficiency reveals that DCs capture allergens and present them to Th2 cells.

TLR4 knockout mice: Reduced response to endotoxins (such as LPS), revealing the association between innate immune recognition and AR.
 

MingCeler Biotech's Tetraploid Complementation Technology
 

Traditional animal model technologies include pronuclear microinjection and ES cell targeting chimera techniques, which adopt a "mouse-to-mouse" model requiring 2-3 generations of breeding to obtain homozygous mice, a process that takes at least 6-8 months or even years. Leveraging its self-developed TurboMice™ technology, MingCeler Biotech has developed multiple disease mouse models. The TurboMice™ technology overcomes the challenges of long modeling cycles and low success rates for complex models. It enables editing at virtually any target gene locus and can generate complete homozygous gene-edited mouse models directly from embryonic stem cells in as little 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!

 

References:

[1] Zhang Ningyuan, Zheng Xijun, Xu Ling, Liu Hongxia, Zheng Qingshan. Disease progression model for Alzheimer's disease and its research progress. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(6): 687-694.

[2] Advances in Clinical Medicine, 2024, 14(7), 1241-1247.

[3] Jin Hong, Peng Yong, Rao Guilan, He Shunqing, Tang Yandan. Research progress in drug therapy for Alzheimer's disease. International Journal of Neurology and Neurosurgery, 2023, 50(1): 87-92.

[4] Mu Yao, Zhao Huimin, Liu Haochen, et al. Recent progress in drug development for Alzheimer's disease. Journal of China Pharmaceutical University, 2024, 55(6): 816-825.

[5] [URL redacted as requested]

[6] Lopes, P.A.; Pádua, M.S.; Guil-Guerrero, J.L. An Overview of Transgenic Mouse Models for the Study of Alzheimer’s Disease. J. Dement. Alzheimer's Dis. 2025, 2, 2. https://doi.org/10.3390/jdad2010002

Special Statement:This article is sourced from the official website of MingCeler Biotech. Personal sharing is permitted. However, media outlets or organizations are strictly prohibited from reprinting or republishing this content on any other platform without prior authorization. For reprint authorization or other cooperation inquiries, please contact: sales@mingceler.com.

Disclaimer: Some materials used are sourced from the internet. If any infringement occurs, please contact us for removal. This article is intended for informational purposes only and does not constitute medical advice or provide treatment recommendations. The views expressed herein do not represent the official stance of MingCeler Biotech, nor do they imply Mingceler Biotech's endorsement or opposition to the opinions presented.