Allergic rhinitis (AR) has become a major chronic respiratory inflammatory disease and is
considered to be one of the global refractory diseases. and it has become an important global
health problem.
The treatment of AR mainly includes environmental control, drug therapy, immunotherapy, etc.
Studies have shown that the positive rate of dust mite allergen skin prick test in AR
patients can reach 70%. Dust mites are considered to be the main allergens causing allergic
diseases such as allergic rhinitis and asthma, which are ubiquitous in clinical living
environments. Since it is difficult for patients to completely avoid exposure to dust mites
in real life, it has attracted more and more attention of scholars to change the allergic
constitution of patients by Specific immunotherapy SIT.
Specific immunotherapy is currently considered to be a more certain therapeutic approach in
addition to allergen avoidance, which is the etiological treatment for IgE-mediated type I
allergic disease. To gradually increase the dose of allergen extracts, gradually induced the
body's immune tolerance, achieve when again contact allergens in patients with symptoms
significantly reduce, or even not occur, the effect of this effect at the end of the
treatment with sustainable for several years, is considered the only can be adjusted by the
immune mechanism to change the allergic disease effective method for treatment of natural
processes, Its safety and efficacy have been proved in clinical treatment by modifying immune
function to change disease progression. Currently, SIT mainly consists of Subcutaneous
immunotherapy (SCIT) and Sublingual immunotherapy (SLIT), which is divided into dose
accumulation and dose maintenance phases. Standardized allergenic vaccines should be used for
immunotherapy. This therapy can significantly reduce the severity of AR, reduce the use of
anti-allergic drugs, and improve the quality of life of many patients. Especially for
children, immunotherapy can not only reduce allergic symptoms, but also prevent the
development of allergic rhinitis to asthma and other severe sensitization reactions.
According to the AR recognition guidelines, immunotherapy is more suitable for patients with
moderate-severe intermittent or persistent AR, especially for those with poor drug treatment
effect.
Compared with SCIT, SLIT is relatively simple to operate, non-invasive, well tolerated and
safe. The risk of systemic adverse reactions is low. In addition, allergen vaccines can be
administered at home by patients or guardians under the guidance of doctors, which reduces
the frequency of hospital visits, thus being highly recommended by clinical practice.
The allergen vaccine of SLIT is mainly dust mite drops in China. The application of
Sublingual immunotherapy of dust mite allergen in the clinical treatment of AR began in 1986.
The way of administration of Sublingual immunotherapy is different from subcutaneous
immunotherapy: allergen vaccine is placed under the tongue, swallowed after several minutes
of absorption, and the vaccine is ingested into the body through the oral mucosa. In 1993,
the European Society of Clinical Immunology and Allergy proposed that sublingual
immunotherapy was safer and more effective than subcutaneous immunotherapy. In 1998, SLIT was
proposed by WHO to be used for adult allergic rhinitis. In 2001, the ARIA group of the World
Health Organization pointed out that SLIT can effectively treat AR and patients can reduce
the use of drugs, which has led to SLIT receiving increasing attention worldwide. In 2013,
the World Allergy Organization (WAO) not only affirmed the clinical efficacy and safety of
SLIT in its position paper, but also recommended SLIT as an initial and early clinical
treatment for allergic diseases. Its application does not need to be based on the premise of
drug treatment failure. Allergen-specific immunotherapy was proposed as the first-line
therapy for AR in the 2015 new edition of Chinese guidelines, which is recommended for
clinical use.
Allergic rhinitis is a non-infectious chronic inflammatory disease of nasal mucosa mainly
mediated by immunoglobulin E (IgE) after atopic individuals are exposed to allergens.
According to the type of allergen, AR can be divided into seasonal and perennial. According
to the course of disease can be divided into intermittent and persistent; The impact on
quality of life is divided into mild and moderate-severe. Current studies have shown that Th1
/ Th2 / Th17 cell immune imbalance is an important mechanism of AR pathogenesis.
In the development of AR, T cells are the only cells that directly react with antigen. Helper
T lymphocytes Th cells are derived from precursor cells that produce InterLeukin-2. After
initial stimulation, these cells develop into Th0 cells (CD4+T cells). It can produce
interferon-γ (IFN-γ), IL-2, IL-4 and IL-5, and Th0 cells can be differentiated into Th1 cells
under the induction of IL-12 and IFN-γ according to the action of cytokines. It secretes
IFN-γ, IL-2 and Tumor necrosis factor β (TNF-β) to participate in cellular immune response.
Under the induction of IL-4, they differentiate into Th2 cells and secrete IL-4, IL-5, IL-13,
IL-8 and other cytokines to participate in humoral immune response. Th17 is a new type of T
helper lymphocyte, which is a pro-inflammatory cell that can activate the body's inflammatory
response and participate in the regulation of the autoimmune system. It was discovered in
2003 and got its name because it can secrete iconic factors such as IL-17 and IL-23, and it
plays an important role in the body's self-immune response.
In the occurrence and development of AR, IFN-γ, IL-4 and IL-17 are the main effectors of Th1,
Th2 and Th17 respectively. It has been reported that IL-4 immune inflammatory factor released
by Th2 cells has a regulatory effect on the level of IgE. However, IFN-γ released by Th1
cells has an inhibitory effect on IL-4 secretion by Th2 cells. Il-17 is a cytokine secreted
by Th17 cells with strong proinflammatory effect. Serum IL-17 in patients is positively
correlated with IgE level, and its increased level can be used as an indicator for the
diagnosis of AR. Therefore, regulating the immune balance of Th1 / Th2 / Th17 cells is an
important way to treat AR. However, increasing evidence shows that innate immune response is
also the pathogenesis of AR.
The innate immune system is the first line of defense against invading pathogens or antigens,
and its response is rapid and non-specific. Subsequently, the activated adaptive immune
system performs complete elimination of specific antigens. Innate lymphoid cells (ILCs), as
an important effector cell population of Innate immunity, are characterized by three major
characteristics: they do not undergo receptor gene rearrangement and clonal selection, lack
of phenotypic markers of myeloid cells and dendritic cells, and their morphology belongs to
the lymphoid lineage. ILCs are mostly tissue-resident lymphocytes, mainly distributed in the
tonsil, broncho-lung, intestinal tract, skin and other mucosal barrier sites. ILCs are
involved in mucosal immune formation, lymphocyte development, tissue damage repair and
epithelial barrier protection, and play an important role in fighting infection, regulating
inflammation and maintaining immune homeostasis.
According to the phenotype and cytokines secreted by ILCs, ILCs can be divided into 3 subsets
of type 1, 2 and 3 innate lymphocytes (ILC1s, ILC2s and ILC3s), which are functionally
approximately corresponding to Th1, Th2 and Th17 of Th cells. ILC1s includes natural killer
cells (NK) and ILC1 cells, which depend on T-box transcription factor (T-BET) and produce
large amounts of interferon (IFN-γ) and tumor necrosis factor-α (TNF-α). The development of
ILC2s depends on the transcription factor GATA3 to produce Th2-type cytokines and other
effector molecules, such as IL-4, IL-5, IL-9, IL-13 and vascular endothelial growth factor
(VEGF), which drive the development of type 2 immune response. Moreover, unlike T cells,
which recognize specific antigens, ILC2s respond to nonspecific cytokines, including IL-25,
IL-33, and Thymic stromal lymphocytes produce hormone. TSLP can stimulate the activation and
proliferation of ILC2s to produce a large amount of IL-5 and IL-13, resulting in airway
inflammation and airway hyperresponsiveness. ILC3s depend on the transcription factor RORTt
to produce cytokines IL-17 and IL-22 similar to Th17.
Some studies have found that after the nasal epithelium of AR patients is stimulated by
allergens, the pro-inflammatory cytokines in the epithelium increase, and IL-25, IL-33 and
TSLP can be detected in the nasal lavage fluid of patients with house dust mite (HDM)
allergy. However, the level of IL-25 released by peripheral blood mononuclear cells (PBMC)
will be up-regulated after basophils of birch and pollen allergy patients are stimulated by
allergens. Have the study showed that the amount of ILC2 in nasal epithelial cells of
patients with allergic fungal sinusitis increased and was positively regulated by IL-25
derived from epithelial cells, which were positively correlated with the expression levels of
IL-5 and IL-13 in nasal mucosa. Other studies have shown that the number of ILC2 in
peripheral blood of patients with HDM allergy is increased, and its number change is
positively correlated with the severity of symptoms. Studies on AR caused by plant allergens
found that during the grass pollen season, the number of ILC2 and ILC3 in peripheral blood of
patients with grass pollen allergy increased, while the number of ILC1 did not change
significantly. However, other study found that the number of ILC2 in peripheral blood of AR
patients did not increase, but that of asthma patients increased. There is no consensus on
whether the number of ILC2s in peripheral blood of AR patients is increased.
In conclusion, the mechanism of AR is mainly related to the imbalance of Th1 / Th2 / Th17
cell immunity, but more and more evidence shows that innate immune response is also the
pathogenesis of AR, and the specific mechanism of ILCs in the development of AR has not been
fully elucidated.
In conclusion, the mechanism of AR is mainly related to the imbalance of Th1 / Th2 / Th17
cell immunity, but more and more evidence shows that innate immune response is also the
pathogenesis of AR, and the specific mechanism of ILCs in the development of AR has not been
fully elucidated. Therefore, this study aims to explore the efficacy of sublingual
desensitization in the treatment of perennial allergic rhinitis and its mechanism of action
on ILCs, reveal the correlation between ILCs (ILC1s, ILC2s, ILC3s) and Th1 / Th2 / Th17 cell
immunity, and provide research basis for clinical research on AR.
