Pathogenesis Of Allergic Diseases Research Articles

Antihistamine therapy in pediatric practice

The article considers the role of histamine in the pathogenesis of allergic diseases and other pathological conditions. The mechanisms that contribute to the development of skin itching are considered separately. The article also shows the role and function of H1-histamine receptor blockers in the treatment of allergic diseases and pseudo allergic reactions. The mechanism of action, indications, contraindications and side effects of the antihistamine therapy are presented. The article also discusses the difference in first and second-generation antihistamines and shows the possible advantages of the first-generation drugs in paediatric practice. The article presents data on the use of dimethindene maleate (Fenistil) in children’s practice, including the use for the relief of skin itching of various genesis.

Effects of Linalyl Acetate on Thymic Stromal Lymphopoietin Production in Mast Cells.

Thymic stromal lymphopoietin (TSLP) is an important factor responsible for the pathogenesis of allergic diseases, such as atopic dermatitis and asthma. Because linalyl acetate (LA) possesses a wide range of pharmacological properties, being antispasmodic, anti-inflammatory, and anti-hyperpigmentation, we hypothesized that LA could inhibit TSLP. Therefore, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, caspase-1 assay, Western blot analysis, fluorescent analyses of the intracellular calcium levels, and the phorbol myristate acetate (PMA)-induced edema model were used to investigate how LA inhibits the production of TSLP in HMC-1 cells. LA reduced the production and mRNA expression of TSLP in HMC-1 cells. LA also inhibited the activation of nuclear factor-κB and degradation of IκBα. PMA plus A23187 stimulation up-regulated caspase-1 activity in HMC-1 cells; however, this up-regulated caspase-1 activity was down-regulated by LA. Finally, LA decreased intracellular calcium levels in HMC-1 cells as well as PMA-induced ear swelling responses in mice. Taken together, these results suggest that LA would be beneficial to treatment of atopic and inflammatory diseases by reducing TSLP.

Does lung microbiome play a causal or casual role in asthma?

Asthma is the most common chronic disease in childhood. The pathogenesis of asthma is multifactorial and is thought to include environmental factors interacting with genetics during pregnancy and in the first years of life. In the last decades, a possible role of gut microbiota in allergic disease pathogenesis has been demonstrated. Next generation sequencing techniques have allowed the identification of a distinct microbiome in the healthy lungs. The lung microbiome is characterized by the prevalence of bacteria belonging to the phylum Bacteroidetes (mostly Prevotella and Veilonella spp) in healthy subjects and to the phylum Proteobacteria in asthmatics (mostly Haemophilus, Moraxella, and Neisseria spp). In asthma, as well as in other diseases, the lung microbiome composition changes due to a disruption of the delicate balance between immigration and elimination of bacteria. The lung microbiome can interact with the immune system, thus influencing inflammation. Early infections with viruses, such as respiratory syncytial virus, may alter lung microbiome composition favoring the emergence of Proteobacteria, a phylum which is also linked to severity of asthma and bronchial hyperreactivity. Lastly, antibiotics may alter the gut and lung microbiota and potentially disturb the relationship between microbiota and host. Therefore, antibiotics should be prescribed with increasing awareness of their potential harmful effect on the microbiota in young children with and without asthma. The potential effects of probiotics and prebiotics on lung microbiome are unknown.

Bleomycin Aggravates Atopic Dermatitis via Lung Inflammation in 2,4-Dinitrochlorobenzene-Induced NC/Nga Mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Bleomycin (BLM) contributes to the induction of pulmonary inflammation and fibrosis in animals. Although skin and lung tissue inflammation is closely related in the pathogenesis of allergic diseases, a proper animal model for investigating the relationship between skin and lung inflammation is lacking. Therefore, we developed a mouse model of AD with relapsing dermatitis and pulmonary fibrosis caused by the administration of allergen and BLM. The present study determined whether lung injury caused by the bronchial application of BLM would exacerbate AD-like allergic inflammation induced by 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. NC/Nga mice treated with BLM and DNCB had increased severity of clinical symptoms and airway hyperresponsiveness as well as increased inflammatory cell infiltration and collagen deposition in the dorsal skin and lung. Compared to normal mice, interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in bronchoalveolar lavage fluid were increased in NC/Nga mice treated with both DNCB and BLM and in animals treated with DNCB alone. Administration of BLM and DNCB increased the levels of IL-4 and IL-13 production in spleen cells and eotaxin-2 mRNA expression in dorsal skin, compared to NC/Nga mice treated with DNCB alone. The total cell numbers in axillary lymph node, bronchoalveolar lavage, and thymus were increased in DNCB-BLM mice compared to those in mice treated with DNCB alone. Administration of BLM and DNCB increased the numbers of cluster of differentiation 4 (CD4)+ T cells and CD11b+granulocyte-differentiation antigen-1 (Gr-1)+ cells among peripheral blood mononuclear cells, CD4+ cells in bronchoalveolar lavage, CD4+ and B220+CD23+ B cells in the axillary lymph node, and CD4+ cells in thymus, compared to DNCB-treated mice. The number of total, CD4+, and CD11b+Gr-1+ cells in the lung were increased in both DNCB and DNCB-BLM mice. These results demonstrate that BLM aggravates allergic skin inflammation and promotes airway hyperreactivity and lung inflammation when combined with DNCB in NC/Nga mice.

Thymus and activation-regulated chemokine (TARC)/CCL17 and IgE are associated with elderly asthmatics

BackgroundThe pathogenesis of asthma, which is an allergic lung disease, is associated with a variety of allergens such as house dust mite, pollen, and mould, IgE containing serum IgE and allergen-specific-IgE, and inflammatory cytokines including thymus and activation-regulated chemokine (TARC)/CCL17. Because aging is an essential factor in the pathogenesis of asthma, we examined biomarkers related to asthmatic subjects depending on age.ResultsPhysiological indices such as FEV1(forced expiratory capacity in 1 s), FEV1 (% predicted), and FEV1/FVC(forced vital capacity) (%) in asthmatic subjects were lower than those in normal subjects. Total IgE, Der p1 specific IgE, and Der f1 specific IgE were elevated in serum of asthmatics relative to normal individuals. Regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5 in serum and interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein (MCP)-1/CCL2, RANTES, and macrophage inflammatory protein (MIP)-1α/CCL3 in bronchoalveolar lavage fluid (BALF) of asthmatic subjects were higher than in normal individuals. Upon classification of experimental groups depending on age, physiological indices and Der p1-specific IgE (class) were decreased in middle aged adult and elderly adult groups relative to the young adult group. TARC levels in serum were strongly elevated in the elderly adult group relative to the young adult and the middle aged adult groups. TARC in serum was related to total IgE in serum in the elderly adult group.ConclusionsTaken together, although TARC in serum and BALF is not different between normal and asthmatic individuals, TARC increases in serum of elderly asthmatic subjects. The level of TARC has a positive effect on the level of IgE in the elderly adult group. These findings may help us better understand the relationship of pathogenesis of allergic diseases and aging.

The Role of Interleukin-31 Polymorphisms in Non-Small Cell Lung Cancer Genetic Susceptibility and Clinical Outcome.

Interleukin-31 (IL-31), a novel T helper type 2 effector cytokine, is known to have an important effect on the pathogenesis of allergic disease and tumors. However, the impact of IL-31 on human lung cancer remains unclear. This study explored the role of IL-31 polymorphisms in lung cancer and sought to characterize how IL-31 polymorphisms correlate with lung cancer tumorigenesis and patient survival rates. Using a single-nucleotide polymorphism genotype assay, we examined the expression of two IL-31 polymorphisms (rs7977932 and rs4758680) in samples from 302 lung cancer patients and 493 control cases. Lung cancer patients who were homozygous CC for rs7977932 or carried the G allele of rs4758680 had significantly poorer prognoses compared to those who did not have these genotypes. Moreover, the rs7977932 CC genotype was significantly associated with metastasis and poor survival status in lung adenocarcinoma. Our study indicates the importance of IL-31 polymorphisms for susceptibility and survival status in lung cancer.

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy

Allergen-specific immunotherapy (AIT) is the mainstay in the treatment of allergic diseases, but the therapeutic effects of AIT need to be improved. CD38+ B cells are an immune cell fraction involved in the pathogenesis of allergic diseases as well as in immune regulation.We sought to elucidate the role of antigen-specific CD38+ B cells in AIT.An analysis was carried out on AIT results of 48 patients with perennial allergic rhinitis (AR), among which peripheral blood immune cells were analyzed by flow cytometry; serum cytokine levels were determined by ELISA. An AR murine model was developed to test the role of CD38+ B cells in AIT.A fraction of antigen-specific CD38+ B cell was detected in AR patients. CD38+ B-cell frequency was negatively correlated with the therapeutic effects of AIT. A negative correlation was detected between the CD38+ B-cell frequency and regulatory T-cell frequency in AR patients treated with AIT. Exposure to specific antigens induced CD38+ B cells to produce IL-6, that converted Treg cells to TH17 cells. Coadministration of anti-CD38 antibody significantly promoted the therapeutic effects of AIT.Antigen-specific CD38+ B cells compromise AIT effects by producing IL-6 to convert regulatory T cells to TH17 cells. Inhibition of CD38+ B cells promotes the effects of AIT.

Phototherapy for neonatal hyperbilirubinemia and childhood eczema, rhinitis and wheeze

The pathogenesis of allergic diseases in childhood may be attributed to influences of early environmental stimuli on fetal and neonatal immune regulation. Neonatal hyperbilirubinemia is common in the Asian population and up to 20% of infants require phototherapy. We examined the hypothesis that phototherapy for neonatal hyperbilirubinemia modulates the infant's risk of developing eczema, rhinitis and wheeze in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort. Interviewers collected information on demographics, lifestyle, birth data andallergic outcomes. Atopic sensitization was assessed through skin prick testing (SPT) to aeroallergens and food allergens. A total of 135 (12.8%) children underwent phototherapy for neonatal hyperbilirubinemia. Infants who underwent phototherapy were of a significantly lower mean (SD) gestational age [37.5 (2.5) weeks] compared to those who did not [38.5 (1.2) weeks p<0.01]. A higher proportion of infants born by Caesarean section underwent phototherapy compared to those who were born vaginally (17.5% vs 10.7%, p<0.01). There were no differences in prevalence of allergen sensitization, eczema, rhinitis and early onset wheeze with use of nebulizer in the first 5 years of life between subjects that underwent phototherapy and those that did not. There were also no associations between mean bilirubin peak levels within the phototherapy group with development of eczema, rhinitis and early onset wheeze in the first 5 years of life. We found no evidence for a link between phototherapy for neonatal hyperbilirubinemia and childhood allergic outcomes in this prospective mother-offspring cohort. NCT01174875 Registered 1 July 2010, retrospectively registered.

Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms

Mast cells represent a crucial cell type in host defense; however, maladaptive responses are contributing factors in the pathogenesis of allergic diseases. Previous work in our laboratory has shown that exposure to silver nanoparticles (AgNPs) results in mast cell degranulation via a non-immunoglobulin E (IgE) mechanism. In this study, we utilized a systems biology approach to identify novel genetic factors playing a role in AgNP-induced mast cell degranulation compared to the classical activation by antigen-mediated FcεRI crosslinking. Mast cell degranulation was assessed in bone marrow-derived mast cells isolated from 23 strains of mice following exposure to AgNPs or FcεRI crosslinking with dinitrophenyl (DNP). Utilizing strain-dependent mast cell degranulation, an association mapping study identified 3 chromosomal regions that were significantly associated with mast cell degranulation by AgNP and one non-overlapping region associated with DNP-mediated degranulation. Two of the AgNP-associated regions correspond to genes previously reported to be associated with allergic disorders (Trac2 on chromosome 1 and Traf6 on chromosome 2) and an uncharacterized gene identified on chromosome 1 (Fam126b). In conjunction, RNA-sequencing performed on mast cells from the high and low responder strains revealed 3754 and 34 differentially expressed genes that were unique to DNP and AgNP exposures, respectively. Select candidate genes include Ptger4, a gene encoding a G-protein coupled receptor in addition to a multifunctional adaptor protein, Txnip, that may be driving mast cell degranulation by AgNP. Taken together, we identified novel genes that have not been previously shown to play a role in nanoparticle-mediated mast cell activation. With further functional evaluation in the future, these genes may be potential therapeutic targets in the treatment of non-IgE mediated mast cell-linked disorders.

Primary atopic disorders.

Monogenic disorders have provided fundamental insights into human immunity and the pathogenesis of allergic diseases. The pathways identified as critical in the development of atopy range from focal defects in immune cells and epithelial barrier function to global changes in metabolism. A major goal of studying heritable single-gene disorders that lead to severe clinical allergic diseases is to identify fundamental pathways leading to hypersensitivity that can be targeted to provide novel therapeutic strategies for patients with allergic diseases, syndromic and nonsyndromic alike. Here, we review known single-gene disorders leading to severe allergic phenotypes in humans, discuss how the revealed pathways fit within our current understanding of the atopic diathesis, and propose how some pathways might be targeted for therapeutic benefit.

Mean Platelet Volume is Increased Only by Subcutaneous Allergen Immunotherapy But not in Allergic Diseases

Objective: Platelets play a role in the pathogenesis of inflammation beside hemostasis. Mean platelet volume (MPV) is used as a biomarker of platelet activation. Although the platelet’s role in the pathogenesis of allergic diseases is well known, the MPV value is still controversial in allergic diseases. The objective is to observe the changes of the MPV value in patients with allergic diseases and patients receiving subcutaneous venom and aeroallergen immunotherapy (SCIT). Materials and Methods: Patients who are followed by our pediatric allergy and immunology clinic were enrolled in the study. The study group included patients with atopic dermatitis, food allergy, chronic urticaria, allergic rhinitis, asthma and obese asthmatics. The control group consisted of age- and gender-matched and otherwise healthy children. The value of MPV was recorded and compared to the control group’s value. The value of MPV was evaluated at the beginning and at the second year of SCIT. Results: Study subgroups included patients with atopic dermatitis (n:132), food allergy (n:47), allergic rhinitis (n:48), chronic urticaria (n:102 ), asthma (n:22), and obese asthmatics (n:31). The value of MPV was not statistically different between the patient and control groups. The severity of atopic dermatitis, autoimmunity of chronic urticaria and presence of obesity in asthmatic patients did not influence the value of MPV. The beginning and the second year median (IQR) MPV levels of the patients receiving SCIT were 7.5 (7.1-8.1) fl and 8.6 (7.6-9.2) fl respectively in the aeroallergen immunotherapy (IT) group, and 7.9 (7.2-8.4) fl and 8.8 (8.3-9.3) fl respectively in the venom immunotherapy (VIT) group (p<0.001). Conclusion: This study has shown that MPV changes significantly over the years in SCIT.

AllerGAtlas 1.0: a human allergy-related genes database.

Allergy is a detrimental hypersensitive response to innocuous environmental antigen, which is caused by the effect of interaction between environmental factors and multiple genetic pre-disposition. In the past decades, hundreds of allergy-related genes have been identified to illustrate the epidemiology and pathogenesis of allergic diseases, which are associated with better endophenotype, novel biomarkers, early-life risk factors and individual differences in treatment responses. However, the information of all these allergy-related genes is dispersed in thousands of publications. Here, we present a manually curated human allergy-related gene database of AllerGAtlas, which contained 1195 well-annotated human allergy-related genes, determined by text-mining and manual curation. AllerGAtlas will be a valuable bioinformatics resource to search human allergy-related genes and explore their functions in allergy for experimental research. Database URL: http://biokb.ncpsb.org/AlleRGatlas/

Decreased CRTH2 Expression and Response to Allergen Re-stimulation on Innate Lymphoid Cells in Patients With Allergen-Specific Immunotherapy.

PurposeGroup 2 innate lymphoid cells (ILC2s) have been implicated in the pathogenesis of allergic disease. However, the effect of allergen-specific immunotherapy (AIT) on ILCs remains to be clarified. The aim of this study was to evaluate the levels of ILC subsets in allergic rhinitis (AR) patients in response to house dust mite (HDM)-specific immunotherapy.MethodsWe enrolled 37 AR patients undergoing AIT (16 responders and 11 non-responders) for 2 years, 35 HDM AR patients and 28 healthy subjects. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry to identify ILC subsets. Stimulation of ILC2s with recombinant allergen-specific protein was used to determine ILC2's activation (CD69 expression).ResultsResponder AIT patients and healthy subjects had a decreased frequency of circulating ILC2s compared to non-responder AIT and AR patients. Conversely, ILC1s from responder AIT patients and healthy subjects showed increased frequency compared to non-responder AIT and AR patients. The frequency of ILC3s natural cytotoxicity receptor (NCR)+ and NCR− in responder AIT patients was significantly lower compared to AR patients and healthy subjects. The ILC1: ILC2 proportion in responder AIT patients was similar to that of healthy subjects. PBMCs from patients who were responders to AIT had a significantly lower expression of the activation marker CD69 on ILC2s in response to allergen re-stimulation compared to AR patients, but no difference compared to non-responder AIT patients and healthy subjects.ConclusionsWe propose that AIT might affect ILC responses. The activation of ILC2s was reduced in AR patients treated with AIT. Our results indicate that a relative ILC1/ILC2 skewed response is a possible key to successful AIT.

Mast Cells in Allergy: The Potential Molecular Targets in the Upstream Signalling Pathways

Mast cells (MCs) play a crucial role in the pathogenesis of allergic diseases, attributable to their hypersensitive reaction to non-harmful substances that elicit an allergic response. As such, by interrupting certain signalling proteins within the signalling pathway of a mast cell, an allergic response may be avoided or inhibited. Compounds that attenuate the release of mediators from mast cells are known as mast cell stabilizers. These drugs are clinically applied to prevent mast cell effector responses towards common allergens. Although commonly prescribed clinical mast cell stabilizers such as disodium cromoglycate and ketotifen fumarate were applied in the preventative treatment of various allergic diseases, there remains a need of advancement of novel mast cell stabilizing drugs that can effectively target specific signalling molecules to provide better treatment option against these diseases. Among these newly discovered potential mast cell stabilizers, much effort has been given to the inhibition of vital upstream signalling molecules such as spleen tyrosine kinase, as well as surface receptors such as the high-affinity IgE receptor (FceRI) and stem cell factor receptor (KIT). A recent study also reported that linker for activation of T cells (LAT) may also be an excellent molecular target for inhibiting mast cell degranulation. Although in most cases the exact mode of action of these molecules is yet to be elucidated, all these compounds have shown mast cell inhibition. Therefore, they might have potential therapeutic use in the treatment of allergies and allergy related diseases where mast cells are majorly involved. Thus, this mini review will focus on summarising the potential signalling molecules or receptors that have been targeted to inhibit mast cell degranulation, particularly those located in the upstream signalling pathway.

A critical role of IL-18 in promoting pathogenesis of allergic diseases

A critical role of IL-18 in promoting pathogenesis of allergic diseases

Role of group 2 innate lymphocytes in aspirin-exacerbated respiratory disease pathogenesis.

Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic eosinophilic nasal polyps, asthma, and airway reactions upon cyclooxygenase (COX) 1 inhibition. AERD is present in up to 7% of adult patients with asthma and the underlying pathogenesis remains largely elusive but prostaglandin D2, cysteinyl leukotrienes, mast cells, and type 2 cytokines are thought to contribute. A wealth of studies have recently implicated group 2 innate lymphoid cells (ILC2), a novel lineage-negative lymphocyte population that produces type 2 cytokines, in human allergic disease pathogenesis. Importantly, our recent work identified that ILC2s are recruited to the nasal mucosa of patients on AERD after COX-1 inhibitor administration. Here, we review the potential impact of ILC2s in the development and propagation of type 2 inflammation in AERD.

Role of Type 2 Innate Lymphoid Cells in Allergic Diseases.

The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis. The growing evidences of the contribution of ILC2 in the induction and maintenance of allergic inflammation in such disease suggest the possibility to target them in therapy. Biological therapies blocking ILC2 activation or neutralizing their effector cytokines are currently under evaluation to be used in patients with type 2-dominated diseases.

TGF-β1 Suppresses IL-33-Induced Mast Cell Function.

TGF-β1 is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGF-β1 can suppress IgE-mediated mast cell activation of human and mouse mast cells. IL-33 is a member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGF-β on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGF-β1, β2, or β3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13, and MCP-1 in a concentration-dependent manner. TGF-β1 inhibited IL-33-mediated Akt and ERK phosphorylation as well as NF-κB- and AP-1-mediated transcription. These effects were functionally important, as TGF-β1 injection suppressed IL-33-induced systemic cytokines in vivo and inhibited IL-33-mediated cytokine release from human mast cells. TGF-β1 also suppressed the combined effects of IL-33 and IgE-mediated activation on mouse and human mast cells. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGF-β1 on IgE-mediated activation, demonstrate that TGF-β1 can provide broad inhibitory signals to activated mast cells.

Beyond epithelial-to-mesenchymal transition: Common suppression of differentiation programs underlies epithelial barrier dysfunction in mild, moderate, and severe asthma.

Epithelial barrier dysfunction is a central feature in the pathogenesis of allergic disease. Epithelial-to-mesenchymal transition (EMT) has been proposed as one mechanism afflicting barrier in asthma. However, genes and pathways involved in aberrant epithelial-mesenchymal signaling, and their relationship to asthma severity, are poorly understood. We used unbiased gene network analysis to evaluate functional convergence in epithelial gene expression signatures across multiple public access transcriptomics datasets of human asthma, followed by text mining to evaluate functional marker relevance of discovered genes. We objectively confirmed these findings in epithelial brushings and primary asthmatic epithelial cells cultured in different biological contexts. We found a striking suppression of epithelial differentiation in asthma, overrepresented by insufficiency in insulin and Notch signaling, but with the absence of conventional EMT markers. We identified EFNB2, FGFR1, FGFR2, INSR, IRS2, NOTCH2, TLE1, and NTRK2 as novel markers central to dysregulation of epithelial-mesenchymal signaling, but surprisingly overlooked in asthma research. We found that this "core" signature of asthma is shared by mild, moderate, and severe forms of disease, progressing with severity. Loss of epithelial differentiation induced by insulin deprivation in normal human bronchial epithelial cells cultured in organotypic conditions closely approximated gene expression in asthmatic epithelial brushings. The comparative analysis of publically available transcriptomes demonstrated that epithelial barrier dysfunction in asthma is characterized by persistent underlying de-differentiation program with complex etiology. The lasting alteration of the asthmatic epithelial cell transcriptome implicates regulation involving metabolism and epigenetics, beyond EMT driven by injury and repair in chronic inflammation.

Type two innate lymphoid cells: the Janus cells in health and disease.

Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease.