REVIEW ARTICLE
OPEN
Pathogenesis of allergic diseases and implications for
therapeutic interventions
Ji Wang1, Yumei Zhou1, Honglei Zhang1, Linhan Hu1, Juntong Liu1, Lei Wang2, Tianyi Wang1, Haiyun Zhang1, Linpeng Cong1 and
Qi Wang1✉
Allergic diseases such as allergic rhinitis (AR), allergic asthma (AAS), atopic dermatitis (AD), food allergy (FA), and eczema are
systemic diseases caused by an impaired immune system. Accompanied by high recurrence rates, the steadily rising incidence rates
of these diseases are attracting increasing attention. The pathogenesis of allergic diseases is complex and involves many factors,
including maternal-fetal environment, living environment, genetics, epigenetics, and the body’s immune status. The pathogenesis
of allergic diseases exhibits a marked heterogeneity, with phenotype and endotype deﬁning visible features and associated
molecular mechanisms, respectively. With the rapid development of immunology, molecular biology, and biotechnology, many
new biological drugs have been designed for the treatment of allergic diseases, including anti-immunoglobulin E (IgE), anti-
interleukin (IL)-5, and anti-thymic stromal lymphopoietin (TSLP)/IL-4, to control symptoms. For doctors and scientists, it is becoming
more and more important to understand the inﬂuencing factors, pathogenesis, and treatment progress of allergic diseases. This
review aimed to assess the epidemiology, pathogenesis, and therapeutic interventions of allergic diseases, including AR, AAS, AD,
and FA. We hope to help doctors and scientists understand allergic diseases systematically.
Signal Transduction and Targeted Therapy  (2023) 8:138 
; https://doi.org/10.1038/s41392-023-01344-4
INTRODUCTION
Allergic diseases are systemic disorders caused by an impaired
immune system. Different allergic diseases, including AR, AAS, AD,
FA and eczema, are caused by complex interactions between
genetic and environmental factors. Allergic diseases are listed by
the World Health Organization (WHO) as one of the top three
disorders to be prevented and controlled in the 21st century. An
allergic disease, whilst a systemic disease, can also manifest as
different local maladies, all of which may lead to anaphylactic
shock in severe cases. The incidence of allergic diseases is high,
bringing much suffering to patients. It is estimated that nearly
500 million and 300 million individuals worldwide have AR and
AAS, respectively,1 with an increasing number of cases. For AAS,
mortality rates in women and men are 90 and 170 per million
individuals, respectively. About 96% of asthma deaths occur in
low-and-middle-income countries.2 It is currently estimated that
FA affects 1–10% of the total population.3 The global prevalence
rate of AD is 8%,4,5 with a lifetime prevalence reaching 20%.6 In
2019, there were 171.17 million patients worldwide with AD.7
Due to the different sites of allergic diseases, the clinical and
pathological manifestations also differ. In AR, after stimulation by
allergens, including airborne dust mites associated with fecal
particles, cockroach remains, pet dander, molds and pollens,
inﬂammatory cells such as mast cells, CD4+ T cells, B cells,
macrophages and eosinophils inﬁltrate the lining of the nasal
cavity, with inﬁltration into the nasal mucosa. T helper 2 (Th2) cells
promote the release of immunoglobulin and cytokines, including
interleukin (IL)-3, IL-4, IL-5, and IL-13; meanwhile, IgE is also
produced by plasma cells. There is, however, still some uncertainty
around the source of IgE production. Follicular helper T (Tfh) cells
are a subpopulation of CD4+ T-effector cells, and in recent years it
has been discovered that the key cells regulating IgE production
are not Th2 cells, but Tfh cells. Allergens cross-link IgE that interact
with mast cells, which further induces the release of multiple
mediators
(including
histamine
and
leukotrienes),
promotes
arteriole dilation and vascular permeability, and causes pruritus,
runny nose, mucus secretion, and pulmonary smooth muscle
contraction.8 Over the next 4–8 hours, the released mediators and
cytokines induce subsequent cellular inﬂammatory reactions (late
inﬂammatory response), leading to the recurrence of symptoms,
often nasal congestion, which generally persist.8,9 The immuno-
pathological proﬁles of AR and AAS are very similar in terms of
eosinophil, mast cell and Th2 cell inﬁltration. Although structural
changes in airway remodeling are well characterized in AAS, they
may also occur in AR. There are also pathophysiological differences
between AR and AAS. In the AAS disease, mucosal pathological
alterations comprise epithelial hyperplasia, goblet cell metaplasia
and increased mucus generation. In the submucosal layer, smooth
muscle hypertrophy, collagen accumulation and large mucus
glands prevail, leading to airway narrowing and enhanced mucus
generation during an asthma attack,10 with symptoms such as
difﬁculty breathing, wheezing, chest pain, and coughing.11 The
pa