image: Natural low-dose allergen exposure on damaged airway epithelium promotes DC and ILC2, which induce Th2 and Tfh cell responses and release of type 2 cytokines. B cells undergo isotype switching to IgE-producing plasma cells and produce IgE under the regulation of type 2 cytokines. Tfh cells induce the development of Bmem through IL-4, IL-9, IL-21, and CD40 ligand–CD40 interaction. cTfh could share properties of memory cells. Allergen–IgE cross-linking of FcεRI receptors on MCs and basophils promotes release of granule-derived mediators such as histamine, tryptase, prostaglandin, leukotrienes and platelet activating factor. AIT induces the generation of DCreg, which stimulates ILC2 transformation to ILCreg and IL10+ ILCs, shift toward Th1 cell response, and Treg proliferation. IL-10, IL-35, and TGF-β secreted by Treg promote the differentiation of Breg cells and IgG/A-producing plasma cells. Tfr cells are a subset of CXCR5+ Foxp3+ Tregs, which downregulate Tfh cell-mediated type 2 immune response. Cytokines (e.g., IL-10, IL-35, IFN-γ, CTLA-4) secreted by ILCreg, IL10+ ILCs, Treg, Breg, Th1 cells, and Tfr inhibit Th2-type responses. IgG1/4 and IgA1/2 competitively inhibit allergen–IgE cross-linking to FcεRI on MCs and basophils, and IgE-facilitated antigen presentation and type 2 cell responses.
Credit: Dr. Yadong Gao from Philipps University of Marburg, Germany
Facing the rising global prevalence of allergic diseases, allergen immunotherapy (AIT)—the only causal treatment capable of modifying the natural course of allergic conditions—has attracted growing attention.
A review titled “Recent Advances in Allergen Immunotherapy” has been published in the Chinese Medical Journal on July 23, 2026, offering a systematic overview of the core mechanisms and key breakthroughs in the field.
The review begins by providing an in-depth analysis of the complex molecular mechanisms underlying AIT-induced long-term immune tolerance. On the adaptive immunity front, AIT modulates T-cell balance, suppresses Th2-type inflammation, and induces regulatory T cells (Tregs) and regulatory B cells (Bregs), while also promoting the secretion of blocking antibodies such as IgG4 and IgA—together forming a multi-layered immunosuppressive network. Notably, the role of innate immunity in AIT has garnered increasing attention in recent years. Studies have revealed that IL-10⁺ ILC2s can mediate the repair of airway epithelial barriers, while phenotypic remodeling of dendritic cells and monocytes suggests that “trained immunity” may be an important contributing mechanism to AIT efficacy. These findings have expanded our understanding of the immune tolerance establishment process from a new perspective.
In terms of therapeutic technologies, the review highlights innovative advances in novel allergen vaccines. Strategies such as recombinant allergen molecule-based hypoallergenic vaccines, virus-like particle-conjugated vaccines, and transgenic rice-based oral vaccines all show promise in maintaining efficacy while reducing the risk of adverse reactions. In addition, innovative administration routes—including intralymphatic immunotherapy (ILIT) and intratonsillar immunotherapy (ITIT)—require only a few injections to complete the treatment course. Preliminary studies have demonstrated favorable safety profiles, though long-term efficacy still awaits validation through large-scale clinical trials.
Addressing the challenge of assessing treatment response in clinical practice, the article systematically reviews practical biomarkers for predicting and monitoring AIT responsiveness, including the sIgE/tIgE ratio, basophil activation test, and IgG4 levels. Drawing on recent randomized controlled trials and real-world studies, the review confirms that AIT significantly alleviates clinical symptoms in patients with allergic rhinitis and asthma, reduces rescue medication use, and lowers the risk of moderate-to-severe acute exacerbations. The study particularly emphasizes AIT's unique disease-modifying effects in preventing asthma onset and blocking new sensitizations—a core advantage that conventional medications cannot replace.
Building on this foundation, the article further explores the synergistic potential of combining AIT with biologics. Research has shown that pretreatment with omalizumab (anti-IgE) can significantly reduce the incidence of systemic adverse reactions to AIT, enabling even patients with severe asthma—previously considered unsuitable—to receive immunotherapy safely. The combination of dupilumab (anti-IL-4/IL-4R) with AIT has also demonstrated promising outcomes in difficult-to-treat asthma and atopic dermatitis, with the complementary mechanisms of the two therapeutic modalities offering the potential to help more patients achieve clinical remission. At the same time, the authors candidly examine the current challenges facing AIT—including the lack of precise indicators for patient selection, adherence issues stemming from the 3- to 5-year treatment duration, and the uneven standardization of allergen extracts—while offering forward-looking perspectives on future directions such as optimizing short-course regimens and developing predictive biomarkers.
This review constructs a comprehensive knowledge framework spanning from basic mechanisms to clinical applications, providing clinicians and researchers with a thorough reference and laying a solid foundation for advancing the precision and broader implementation of AIT in clinical practice.
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Reference
Title of original paper: Recent advances in allergen immunotherapy
Journal: Chinese Medical Journal
DOI: https://doi.org/10.1097/CM9.0000000000004189
About Dr. Wei Fu from Zhongnan Hospital of Wuhan University, China, and Dr. Yadong Gao from Philipps University of Marburg, Germany
First author: Wei Fu, M.D., attending physician, Department of Allergy, Zhongnan Hospital of Wuhan University, Wuhan, China.
Corresponding author: Yadong Gao, M.D., Ph.D. (Philipps University of Marburg, Germany), Chief Physician and Director of the Department of Allergy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. He has long been engaged in the clinical diagnosis and management of allergic diseases, including allergic asthma, allergic rhinitis, and urticaria, with particular expertise in allergen immunotherapy and the management of severe allergic reactions.
Funding information
None
Journal
Chinese Medical Journal
Method of Research
Systematic review
Subject of Research
Not applicable
Article Title
Recent advances in allergen immunotherapy
Article Publication Date
23-Jul-2026
COI Statement
None