Regulation Of Allergic Inflammation Research Articles

Allergic inflammation in lungs and nasal epithelium of rat model is regulated by tissue-specific miRNA expression

IntroductionAtopic asthma and allergic rhinitis are common chronic inflammatory diseases affecting lower airways and nasal mucosa, respectively. Several reports demonstrated frequent co-occurrence of these two diseases, however, the exact molecular mechanism has not been described. The present study aimed to investigate if small non-coding RNA might be responsible for the co-occurrence of asthma and allergic rhinitis in an animal model of allergic airway inflammation. Materials and methodsAs an in vivo model of allergic airway inflammation, we used Brown Norway rats exposed intranasally to house dust mite (HDM). Histological analysis, total IgE concentration, eosinophil counts and iNOS gene expression were determined to confirm inflammatory changes. Small RNA sequencing in the lung tissue and nasal epithelium was performed with TruSeq Small RNA Library Preparation Kit and analyzed using the BaseSpace tool. Validation of sequencing results was performed using qPCR. To assess the functional role of hsa-miR-223–3p, we transfected normal human bronchial epithelial (NHBE) cells with specific LNA-inhibitor and measured phosphorylated protein level of NF-kB with ELISA. Expression analysis of NF-kB pathway-related genes was performed using qPCR with SYBR Green and analyzed in DataAssist v3.01. Statistical analysis were done with STATISTICA version 13. ResultsWe found 9 miRNA genes differentially expressed in the lungs of allergic rats. In nasal epithelium, only rno-miR-184 was upregulated in animals exposed to HDM. Validation with qPCR confirmed increased expression only for rno-miR-223–3p in the lungs from allergic rats. The expression of this miRNA was also increased in normal bronchial epithelial ALI cell culture stimulated with IL-13, but not in cells cultured in monolayer due to the low mRNA level of IL13RA1 and IL13RA2. Transfecting NHBE cells with hsa-miR-223–3p inhibitor increased the amount of phosphorylated NF-kB protein level and expression of MUC5AC, CCL24 and TSLP genes. ConclusionsThese findings suggest that miRNAs that regulate allergic inflammation in the lungs and nasal epithelium are specific for upper and lower airways. Furthermore, our study provides new insight on the role of hsa-miR-223–3p, that via targeting NF-kB signaling pathway, regulates the expression of MUC5AC, CCL24 and TSLP. Taken together, our study suggests that miR-223–3p is a regulator of allergic inflammation and could potentially be used to develop novel and targeted therapy for asthma.

Functional role of histamine receptors in the renal cortical collecting duct cells.

Histamine is an important immunomodulator, as well as a regulator of allergic inflammation, gastric acid secretion, and neurotransmission. Although substantial histamine level has been reported in the kidney, renal pathological and physiological effects of this compound have not been clearly defined. The goal of this study was to provide insight into the role of histamine-related pathways in the kidney, with emphasis on the collecting duct (CD), a distal part of the nephron important for the regulation of blood pressure. We report that all four histamine receptors (HRs) as well as enzymes responsible for histamine metabolism and synthesis are expressed in cultured mouse mpkCCDcl4 cells, and histamine evokes a dose-dependent transient increase in intracellular Ca2+ in these cells. Furthermore, we observed a dose-dependent increase in cAMP in the CD cells in response to histamine. Short-circuit current studies aimed at measuring Na+ reabsorption via ENaC (epithelial Na+ channel) demonstrated inhibition of ENaC-mediated currents by histamine after a 4-h incubation, and single-channel patch-clamp analysis revealed similar ENaC open probability before and after acute histamine application. The long-term (4 h) effect on ENaC was corroborated in immunocytochemistry and qPCR, which showed a decrease in protein and gene expression for αENaC upon histamine treatment. In summary, our data highlight the functional importance of HRs in the CD cells and suggest potential implications of histamine in inflammation-related renal conditions. Further research is required to discern the molecular pathways downstream of HRs and assess the role of specific receptors in renal pathophysiology.

The current state of the problem with the diagnosis and treatment of allergic rhinitis in pediatric practice

Among all allergic diseases in pediatric practice, allergic rhinitis is one of the most common pathologies of the upper respiratory tract. This review deals with the problem of modern principles for the diagnosis and treatment of allergic rhinitis in children based on the analysis of literature sources using electronic databases PubMed, Web of Science, MedLine, the Cochrane Library. Allergic rhinitis is an important medical and social problem of our time the importance of which has increased significantly in recent years. The growing number of people sensitized to pollen, the variety of symptoms and the negative impact on the quality of life of patients make pollen allergy one of the major problems in pediatrics. Despite the development of international national protocols and clinical guidelines, in many countries the control of allergic rhinitis in children remains insufficient. Therefore, it is necessary to take into account the individual characteristics of patients, pay attention to both nasal and extranasal symptoms, consider all pathognomonic diagnostic aspects, because the underdiagnosis of this allergic disease leads to inadequate therapy, complications, more severe atopy and reduced quality of children’s life in general. Recently, there is growing evidence of the need for personalized selection of the most effective therapy for allergic rhinitis in children. In-depth study of the pathogenetic role of circadian molecular clock in children with seasonal allergic rhinitis using informative molecular genetic methods may allow characterizing in detail the mechanism of regulation of allergic inflammation of the upper airway mucosa and evaluating the role of circadian genes in the development of allergic diseases, in particular allergic rhinitis. In the future, these studies may become an alternative to improve control over the course of allergy and the organization of a comprehensive monitoring system, development of new strategies for the treatment and prevention of allergic rhinitis in children.

Asthma, allergy and vitamin E: Current and future perspectives

Asthma and allergic disease result from interactions of environmental exposures and genetics. Vitamin E is one environmental factor that can modify development of allergy early in life and modify responses to allergen after allergen sensitization. Seemingly varied outcomes from vitamin E are consistent with the differential functions of the isoforms of vitamin E. Mechanistic studies demonstrate that the vitamin E isoforms α-tocopherol and γ-tocopherol have opposite functions in regulation of allergic inflammation and development of allergic disease, with α-tocopherol having anti-inflammatory functions and γ-tocopherol having pro-inflammatory functions in allergy and asthma. Moreover, global differences in prevalence of asthma by country may be a result, at least in part, of differences in consumption of these two isoforms of tocopherols. It is critical in clinical and animal studies that measurements of the isoforms of tocopherols be determined in vehicles for the treatments, and in the plasma and/or tissues before and after intervention. As allergic inflammation is modifiable by tocopherol isoforms, differential regulation by tocopherol isoforms provide a foundation for development of interventions to improve lung function in disease and raise the possibility of early life dietary interventions to limit the development of lung disease.

Цитокины в иммунопатогенезе аллергии

Allergy is characterized by inadequate hyperimmune response to one or several antigens with the properties of allergens. A specific pattern of abnormal synthesis of some cytokines (principal molecular mediators of the initiation, development, and regulation of allergic inflammation) has an important pathogenic role in allergy. In recent years, it is generally accepted that allergic disorders are accounted for by impaired immune regulation resulting from increased imbalanced activation of allergen-specific T helper 2 cell clones. Allergic type of immune response is currently referred to as type 2 immune response which normally provides humoral immunity, anthelmintic protection etc. However, pathological response results in allergy. Studies on immune pathogenesis of allergic disorders have improved our understanding of the role of altered synthesis of some cytokines (key mediators of allergic inflammation). Cytokines involved in the initiation and regulation of allergy are produced by epithelial cells, various subsets of leukocytes, innate lymphoid cells, and allergen-activated T helper cell clones. Analysis of the associations of the changes in immune reactivity and clinical manifestations has established pathogenic heterogeneity and identified asthma phenotypes and endotypes. These findings have provided a basis for more reasonable, successful, and personalized approach to biological anti-cytokine treatment for allergic disorders. KEYWORDS: allergy, cytokines, T helper cell clones, phenotype, asthma, anti-cytokine therapy. FOR CITATION: Simbirtsev A.S. Cytokines and their role in immune pathogenesis of allergy. Russian Medical Inquiry. 2021;5(1):32–37. DOI: 10.32364/2587-6821-2021-5-1-32-37.

B regulatory cells in allergy.

B cells have classically been recognized for their unique and indispensable role in the production of antibodies. Their potential as immunoregulatory cells with anti-inflammatory functions has received increasing attention during the last two decades. Herein, we highlight pioneering studies in the field of regulatory B cell (Breg) research. We will review the literature on Bregs with a particular focus on their role in the regulation of allergic inflammation.

Ginger Increases ALDH1A1 Expression and Enhances Retinoic Acid Signaling in a Human Colonic Epithelial Cell Line.

Aldehyde dehydrogenase 1A1 (ALDH1A1) in intestinal epithelial cells (IECs) plays a critical role in regulating immune responses through the production of retinoic acid (RA). However, little is known about its regulation by dietary components. We previously demonstrated that kakkonto, a Japanese traditional herbal medicine, and its constituent puerarin induce the expression of ALDH1A1 mRNA in colonic IECs and thereby attenuate food allergy symptoms in mice. This study aims to investigate the cellular responses of IECs to ALDH1A1 expression as a result of natural food components. The seven medicinal herbs that compose kakkonto were used to treat cultured an IEC line: Caco-2 cells. Expressions levels of ALDH1A1 were analyzed in Caco-2 cells by quantitative RT-PCR, immunocytochemistry and western blotting. Ginger increased the expression levels of ALDH1A1 mRNA and protein in Caco-2 cells. In addition, ginger significantly upregulated the gene expression of retinoic acid receptor (RAR) alpha (RARA), thereby enhancing RA signaling. Furthermore, ginger downregulated the expression of histone deacetylase (HDAC)2 (HDAC2) and HDAC3 in Caco-2 cells. The present study suggests the possibility that food ingredients such as a ginger modulate vitamin A metabolism in the gut through the regulation of RA synthesis, which may contribute to RA-mediated regulation of immune responses and the regulation of allergic inflammation.

Regulation of allergic inflammation by dendritic cells.

Dendritic cells are critical in directing inflammatory versus tolerogenic responses. As the burden of allergic disease rises worldwide, increased understanding of mechanisms underlying these diseases is needed. This review highlights research demonstrating how dendritic cells influence allergic disease development, providing important mechanistic insights into current clinical management strategies as well as potential areas of focus for future development of novel therapeutic strategies. Recent studies continue to elucidate dendritic cell-associated pathways which can either promote or prevent allergic inflammation. Mechanisms involved include various aspects of dendritic cell activity, from antigen sampling and dendritic cell migration to complex dendritic cell interactions with other immune cells, infectious agents and allergens. A deeper understanding of these mechanisms and how dendritic cells promote tolerance provides insight into potential strategies to therapeutically target dendritic cells in the management of allergic disease. Recent discoveries illustrate crucial roles of dendritic cells as regulators of inflammatory versus tolerant cascades. Building on lessons from oncologic strategies for harnessing dendritic cells to promote antitumor responses, several novel pathways could also be targeted to promote dendritic cell-mediated tolerogenesis in the context of allergy. Additional studies are needed to further define the roles and potential effects of dendritic cells in these potential strategies to reduce allergic inflammation.

Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice.

The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.

IL-27 targets Foxp3+ Tregs to mediate antiinflammatory functions during experimental allergic airway inflammation.

Foxp3+ CD4 Tregs are central regulators of inflammation, including allergic inflammation in the lung. There is increasing evidence that inflammatory factors undermine adequate Treg functions and homeostasis, resulting in prolonged and exacerbated inflammation. Therefore, identifying the factors is of the utmost important. IL-27 is an antiinflammatory cytokine implicated in immune regulation and tolerance. However, the cellular mechanisms underlying IL-27-mediated immune regulation in vivo remain largely unknown. Utilizing a cockroach antigen-induced allergic inflammation model in mice, we sought to test the roles of Tregs during IL-27-mediated regulation of allergic inflammation. Intranasally delivered IL-27 significantly reduced the development of airway inflammation. Unexpectedly, the IL-27-induced reduction occurred only in the presence of Tregs. Il27ra-/- and Treg-specific Il27ra-/- mice developed severe airway inflammation, and IL-27 treatment had little impact on diminishing the inflammatory responses. IL-27-induced treatment was restored following transfer of WT Tregs but not of Tregs deficient in Lag3, a molecule induced by IL-27 in Tregs. Finally, Tregs from asthmatic patients exhibited blunted STAT1 phosphorylation following IL-27 stimulation. Taken together, our results uncover that Tregs are the primary target cells of IL-27 in vivo to mediate its antiinflammatory functions, suggesting that altered IL-27 responsiveness in Tregs may underlie inadequate Treg functions and perpetuation of inflammation.

Identification of Functionally Relevant microRNAs in the Regulation of Allergic Inflammation.

Transgenic methods to manipulate CD4 T lymphocytes in vivo via forced expression of TCR transgenes and targeted "knockout" of individual genes by Cre-lox technology are fundamental to modern immunology. However, efforts to scale up functional analysis by modifying expression of larger numbers of genes in T cells ex vivo have proven surprisingly difficult. Early RNA interference experiments achieved successful small RNA transfection by using very high concentrations of short-interfering RNA (siRNA) [1], but primary T cells are generally resistant to standard electroporation, cationic liposome-, and calcium phosphate-mediated transfection methods. Moreover, although viral vectors can successfully introduce DNA fragments of varying length, expression of these constructs in primary T cells is low efficiency and the subcloning process laborious. In this context, the relatively recent discovery of dozens of highly expressed microRNAs (miRNAs) in the immune system provides both an opportunity and a new challenge [2, 3]. How can we query the miRNAome of a cell to assign particular roles to individual miRNAs? Here, we describe an optimized technique for efficient and reproducible transfection of primary mouse CD4 T cells in vitro with synthetic miRNA mimics.

Regulation of allergic inflammation by the ectoenzyme E-NPP3 (CD203c) on basophils and mast cells.

Adenosine 5'-triphosphate (ATP) is released from dying or damaged cells, as well as from activated cells. Once secreted, extracellular ATP induces several immune responses via P2X and P2Y receptors. Basophils and mast cells release ATP upon FcεRI-crosslinking, and ATP activates basophils and mast cells in an autocrine manner. Nucleotide-converting ectoenzymes, such as E-NTPD1, E-NTPD7, and E-NPP3, inhibit ATP-dependent immune responses by hydrolyzing ATP, thereby contributing to immune response regulation. E-NPP3 is a well-known activation marker for human basophils. E-NPP3's physiologic function has recently been disclosed in mice. E-NPP3 is rapidly induced on basophils and mast cells after FcεRI-crosslinking and hydrolyzes extracellular ATP on cell surfaces to prevent ATP-dependent excess activation of basophils and mast cells. In the absence of E-NPP3, basophils and mast cells are overactivated and mice suffer from severe chronic allergic inflammation. Thus, the ATP-hydrolyzing ectoenzymes E-NPP3 has a nonnegligible role in the regulation of basophil- and mast cell-mediated allergic responses.

Modulation of the allergic response by dietary carotenoids

SummaryCarotenoids are isoprenoid pigments naturally present in high concentrations in most vegetables — for example, avocados, papayas, tomatoes and carrots—, but they also can be found as additives and dyes found in various meat products, vegetable oils, sauces, dressings, meals, among others.In recent years, some studies have reported that dietary carotenoids participate in many pathophysiological processes, including the allergic immune response. Prevalence rates for these diseases have had an alarming increase over the past five decades in a world scale, at the same time, a number of factors and assumptions in attempt to explain this phenomenon have been proposed, one of them being the diet hypothesis, which states that the composition of several micro and macronutrients of food, as well as changes in dietary patterns, would had some influence in such problematic.Arising epidemiological and basic experimental evidence indicates that dietary carotenoids are involved in the regulation of allergic inflammation and thus are postulated as adjuvants in these diseases treatment. In this paper the authors will review the state of art in relation to the effects of dietary carotenoids on the allergic condition.

Regulation of allergic inflammation by murine endothelial cell transglutaminase 2 (HYP7P.260)

Abstract Tissue transglutaminase 2 (TG2) is a multifunctional enzyme that is involved in inflammatory processes. In allergic inflammation, previous research indicates that TG2 is upregulated in human asthma and in the lung endothelium of OVA-challenged mice. We hypothesized that endothelial cell TG2 is required for allergic inflammation. To test this hypothesis, we generated mice in which TG2 was specifically deleted in the endothelium using the Cre-Lox recombinase system. To induce allergic inflammation, mice were sensitized and challenged with OVA. Compared to wild type mice challenged with OVA, OVA-challenged TG2 knockout mice exhibited a significant reduction in lung airway resistance, the number of eosinophils in the BAL, and the number of eosinophils in the airway spaces. Endothelial deletion of TG2 did not affect chemokines and cytokines that regulate allergic inflammation. Taken together, these findings indicate that endothelial cell TG2 is required for allergic inflammation. This suggests that TG2 regulates the recruitment of eosinophils into OVA-challenged lungs. Future studies will focus on identifying mechanisms by which TG2 regulates signals for leukocyte recruitment during allergic lung inflammation.

Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils

Sexual dimorphism in asthma links the estrogen and allergic immune responses. The function of estrogen was classically believed to be mediated through its nuclear receptors, i.e., estrogen receptors (ERs). However, recent studies established the important roles of G-protein-coupled estrogen receptor (GPER/GPR30) as a novel membrane receptor for estrogen. To date, the role of GPER in allergic inflammation is poorly understood. The purpose of this study was to examine whether GPER might affect the functions of eosinophils, which play an important role in the pathogenesis of asthma. Here, we demonstrated that GPER was expressed in purified human peripheral blood eosinophils both at the mRNA and protein levels. Although GPER agonist G-1 did not induce eosinophil chemotaxis or chemokinesis, preincubation with G-1 enhanced eotaxin (CCL11)-directed eosinophil chemotaxis. G-1 inhibited eosinophil spontaneous apoptosis and caspase-3 activities. The anti-apoptotic effect was not affected by the cAMP-phospodiesterase inhibitor rolipram or phosphoinositide 3-kinase inhibitors. In contrast to resting eosinophils, G-1 induced apoptosis and increased caspase-3 activities when eosinophils were co-stimulated with IL-5. No effect of G-1 was observed on eosinophil degranulation in terms of release of eosinophil-derived neurotoxin (EDN). The current study indicates the functional capacities of GPER on human eosinophils and also provides the previously unrecognized mechanisms of interaction between estrogen and allergic inflammation.

MicroRNA-155 is essential for TH2-mediated allergen-induced eosinophilic inflammation in the lung

Allergic asthma is a chronic disease of the conducting airways characterized by T(H)2 inflammation and tissue remodeling after exposure to inhaled allergens. Although the T(H)2 profile is undisputed, the underlying molecular mechanisms leading to this abnormal T(H)2 profile remain largely unclear. MicroRNAs (miRNAs) are short noncoding RNAs that are important regulators of gene expression in the immune system. However, the role of miRNAs, specifically miR-155, in the regulation of allergic airway inflammation is unexplored. We sought to assess the contribution of miR-155 in a mouse model of allergic airway inflammation. To investigate a role for miR-155 in the regulation of allergic inflammation in vivo, we used miR-155 knockout (KO) and wild-type (WT) mice sensitized and exposed to ovalbumin. miR-155 deficiency resulted in diminished eosinophilic inflammation and mucus hypersecretion in the lungs of allergen-sensitized and allergen-challenged mice compared with WT control animals. This was supported by a reduction in T(H)2 cell numbers and airway T(H)2 cytokine levels and complete abrogation of allergen-induced airway eotaxin-2/CCL24 and periostin levels in miR-155 KO mice. Intranasal instillation of eotaxin-2/CCL24 before allergen challenge partially restored airway eosinophilia in miR-155 KO mice, and adoptive transfer of CD4(+) T cells resulted in a similar degree of airway eosinophilia in miR-155 KO and WT mice. Furthermore, the transcription factor PU.1, a negative regulator of T(H)2 cytokine production, was upregulated in the airways of allergen-challenged miR-155 KO mice compared with WT mice. Our data provides evidence that miR-155 contributes to the regulation of allergic airway inflammation by modulating T(H)2 responses through the transcription factor PU.1.

The emerging role of interleukin-21 in allergic diseases (Review)

Interleukin (IL)-21 is a newly discovered member of the type I cytokine family. Since its discovery in 2000, IL-21 has been the focus of extensive investigation, due to its homology to IL-2, IL-4 and IL-15 and its pleiotropic effects on innate and adaptive immune responses. An increasing amount of experimental evidence supports a role for IL-21 in the pathogenesis of several allergic diseases, such as allergic rhinitis, atopic dermatitis (AD) and atopic asthma. In this review, we aimed to discuss the biological characteristics of IL-21 and summarize the current progress on the role of IL-21 in the regulation of allergic inflammation.

Glutathione S‐transferase P1 Ile105Val polymorphism modulates allergen‐induced airway inflammation in human atopic asthmatics in vivo

Glutathione S-transferase P1 is a Phase II cytoprotective and detoxifying enzyme that is widely expressed in human airways. The glutathione S-transferase P1 Ile105Val polymorphism has been linked with atopic disorders and asthma. Yet, little remains known about the regulation of allergic inflammation by glutathione S-transferase P1 in human asthmatics. To establish the effect of the glutathione S-transferase P1 Ile105Val polymorphism on allergen-induced airway inflammation and oxidant stress, and non-specific bronchial hyperresponsiveness to methacholine and reactivity to specific allergen in mild human atopic asthmatics in vivo. Five Val(105)/Val(105) , twelve Val(105)/Ile(105) and twenty Ile(105)/Ile(105) mild atopic asthmatics underwent methacholine challenge, inhaled allergen challenge and endobronchial allergen provocation through a bronchoscope. A panel of inflammatory cytokines and chemokines, F2 -isoprostanes and isofuranes, markers of oxidative stress, thromboxane B2 and immunoglobulin E were measured in bronchoalveolar lavage fluid at baseline and 24 h after allergen instillation. Asthmatics with glutathione S-transferase P1 Val(105)/Val(105) compared with asthmatics with the glutathione S-transferase P1 Val(105)/Ile(105) and Ile(105)/Ile(105) had greater generation of acute phase cytokines (TNF-α, IL-6, CXCL8), IL-12, CCL11, thromboxane B2 and immunoglobulin E at 24 h after local allergen challenge. The GSTP1 genotype had no effect on airway hyperresponsiveness to methacholine and the reactivity to specific allergen. The glutathione S-transferase P1 Ile105Val polymorphism markedly modifies allergen-provoked airway inflammation in atopic asthmatics in vivo. Modulation of the biochemical milieu in response to allergen provides a mechanistic explanation for regulatory effects of glutathione S-transferase P1 polymorphism on airway pathophysiology, and may guide improvement of future therapeutic methods in human atopic asthmatics. These findings must me confirmed in a larger study population of asthmatics with various ethnicities.

News in the pathophysiology of asthma

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Contribution of interleukin 17A to the development and regulation of allergic inflammation in a murine allergic rhinitis model

BackgroundInterleukin (IL) 17A, a key cytokine of TH17 cells, is a well-known proinflammatory cytokine. Despite the important role of TH17 cells in acute airway inflammation, the role of IL-17A in allergic rhinitis (AR) remains unclear. ObjectiveTo investigate the role of IL-17A in the allergic response in AR. MethodsWild-type BALB/c and IL-17A–deficient mice were immunized intraperitoneally and were challenged intranasally with ovalbumin. Allergic symptom scores, eosinophil infiltration, serum IgE level, and the levels of several cytokines in nasal lavage fluid and splenocyte supernatants were analyzed. ResultsIL-17A levels increased significantly more in ovalbumin-sensitized wild-type mice than in the negative control group. IL-17A–deficient mice showed a significant decrease in allergic symptoms, serum IgE levels, and eosinophil infiltration into the nasal mucosa compared with wild-type mice. IL-17A–deficient mice also showed decreased histamine and cysteinyl leukotriene release. Bone marrow–derived mast cells from IL-17A–deficient mice showed significantly lower degranulation and secretion of tumor necrosis factor α. Moreover, IL-17A deficiency attenuated the IL-5 level in nasal lavage fluid and its production in response to ovalbumin but did not increase interferon γ production and its level in nasal lavage fluid. In addition, secretion of IL-17A from spleen cells induced the expression of proinflammatory cytokine messenger RNA in macrophages. The mean level of proinflammatory cytokines, including tumor necrosis factor α and IL-17, decreased in IL-17A–deficient mice. ConclusionThese results suggest that IL-17A may partly contribute to the development of nasal allergic inflammation in an AR animal model and regulate AR via the activation of proinflammatory cytokines and modulation of TH2 cytokine.