Allergic Inflammatory Diseases Research Articles

Mesenchymal stromal cells and their small extracellular vesicles in allergic diseases: From immunomodulation to therapy.

Mesenchymal stromal cells (MSCs) have long been considered a potential tool for treatment of allergic inflammatory diseases, owing to their immunomodulatory characteristics. In recent decades, the medical utility of MSCs has been evaluated both in vitro and in vivo, providing a foundation for therapeutic applications. However, the existing limitations of MSC therapy indicate the necessity for novel therapies. Notably, small extracellular vesicles (sEV) derived from MSCs have emerged rapidly as candidates instead of their parental cells. The acquisition of abundant and scalable MSC-sEV is an obstacle for clinical applications. The potential application of MSC-sEV in allergic diseases has attracted increasing attention from researchers. By carrying biological microRNAs or active proteins, MSC-sEV can modulate the function of various innate and adaptive immune cells. In this review, we summarise the recent advances in the immunomodulatory properties of MSCs in allergic diseases, the cellular sources of MSC-sEV, and the methods for obtaining high-quality human MSC-sEV. In addition, we discuss the immunoregulatory capacity of MSCs and MSC-sEV for the treatment of asthma, atopic dermatitis, and allergic rhinitis, with a special emphasis on their immunoregulatory effects and the underlying mechanisms of immune cell modulation.

Recent Advances in the Treatment of Eosinophilic Esophagitis.

Eosinophilic esophagitis is an increasingly common inflammatory allergic disease of the esophagus characterized by esophageal eosinophilia and symptoms of esophageal dysfunction. The therapeutic landscape has rapidly evolved for this emerging type 2 inflammatory disorder. We review traditional therapies including updates and expert opinions in addition to promising therapies on the horizon and the history of therapies that failed to meet end points and highlight knowledge gaps for future investigations.

Ethical Implications of Continuing Oral Immunotherapy After the Development of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease requiring maintenance therapy. Traditionally, EoE has been a contraindication to oral immunotherapy (OIT) and a rationale for discontinuing treatment because OIT may induce EoE. Most, but not all patients with OIT-induced EoE experience symptom resolution and histologic remission after discontinuing OIT. Recent studies report OIT continuation even after EoE onset, despite the previously accepted standard of care. This creates clinical as well as ethical challenges for allergists treating these patients. Considering the published literature on EoE and OIT and the primary medical ethics principles of beneficence, nonmaleficence, autonomy, and justice, we discuss the ethical implications of pursuing desensitization despite the potential complications associated with EoE. When ethical principles are in opposition, shared decision-making should be employed to determine whether OIT should be continued after an EoE diagnosis. This article highlights the ethical dilemmas allergists face when determining whether patients with a diagnosis of EoE should continue OIT.

Natural killer cells contribute to ‘hot’ tumor regression in the allergic inflammatory environment

Systemic immune status influences the elimination of tumor cells. However, it remains unclear how chronic inflammation in allergic diseases affects the tumor microenvironment and tumorigenesis. To investigate tumor progression in a state of heightened allergic inflammation, we established a mouse model of allergic inflammation. We used house dust mite extract to induce a hyper-reactive systemic immune response. Additionally, we subcutaneously inoculated two types of cancer cells (CT26 and 4T1 tumors). We conducted immune profiling of the ex-vivo tumor mass using multicolor flow cytometry staining and performed dynamic analysis of peripheral cytokines to explore the significant relationship between the development of allergic inflammation and tumorigenesis. We found that mice in a state of allergic inflammation were more susceptible to developing tumors. Interestingly, the growth of T cell-inflamed was inhibited in the allergic state, while growth of non-T cell-inflamed was promoted. Further research revealed that natural killer (NK) cells with enhanced tumor-killing or immune-regulating abilities were more active in “ hot ” tumors. Inhibiting NK cell activity can partially alleviate the impact of allergic inflammation on tumor growth. In summary, our results suggest that NK cells play significant role in suppressing tumor growth in an allergic inflammation mouse model. This phenomenon seems to be closely linked to both the inherent characteristics of the tumor and its interaction with the immune system. The innate immune system can be mobilized to synergize with the adaptive immune system to inhibit tumor growth, which opens a new way for a tumor immunotherapy.

Black Ginseng Extract Exerts Potentially Anti-Asthmatic Activity by Inhibiting the Protein Kinase Cθ-Mediated IL-4/STAT6 Signaling Pathway.

Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCθ) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCθ and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCθ and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma.

Phyllostachys nigra Munro var alleviates inflammatory chemokine expression and DNCB-induced atopic-like dermatitis in BALB/c mice

Ethnopharmacological relevancePhyllostachys nigra (PN) is an herbal medicine that originates from the inner bark of Phyllostachys nigra Munro var. henosis Stapf or Phyllostachys bambusoides Siebold et Zuccarini. It has long been used to relieve fever and to treat diarrhea and inflammation. PN has been shown to possess inhibitory effects on pneumonia, intestinal inflammation, tumors, and fatigue. However, its potential efficacy in the treatment of atopic dermatitis (AD) has not been extensively studied or reported. Aim of the studyThe objective of this research was to investigate the impact of PN on HaCaT and HMC-1 cells, as well as its potential in an experimental model of AD induced by 1-chloro-2,4-dinitrobenzene (DNCB). MethodsWe analyzed the anti-inflammatory efficacy of PN in HaCaT cells and HMC-1 cells using ELISA and PCR, and investigated invasion of inflammatory cell, change of dermis and epidermis, and the SCORAD index in AD-like mice model. We also measured the MAPK signaling pathway using the dorsal tissue of mice. ResultsOur results show that PN reduced the expressions of TARC, GM-CSF, TNF-α, MCP-1, and IL-6 in vitro. PN also decreased the SCORAD index, thickening of epidermis and dermis, and inhibited the invasions of mast cells and eosinophils as well as CD4+ T and CD8+ T cells. Furthermore, PN suppressed the level of IgE and IL-6, and also inhibited the MAPK phosphorylation in the dorsal skin. ConclusionThese results demonstrate that PN could be an effective alternative medicine for allergic inflammatory disease.

Role of Serum/Glucocorticoid-Regulated Kinase 1 (SGK1) in Immune and Inflammatory Diseases.

Serum/glucocorticoid-regulated kinase 1 (SGK1), a member of the serine/threonine protein kinase gene family, is primarily regulated by serum and glucocorticoids. SGK1 is involved in the development of tumors and fibrotic diseases. However, relatively little research has been conducted on their role in immune and inflammatory diseases. SGK1 may act as a pivotal immune regulatory gene by modulating immune cells (e.g., T cells, macrophages, dendritic cells, and neutrophils) and functions and is involved in the pathogenesis of some immune and inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis, allergic diseases, sepsis, and major depressive disorder. This review aims to provide an overview of the latest research focusing on the immune and inflammatory regulatory roles of SGK1 and provide new insights into diagnostic and therapeutic approaches for immune and inflammatory diseases.

Crosstalk between the gut microbiota and innate lymphoid cells in intestinal mucosal immunity.

The human gastrointestinal mucosa is colonized by thousands of microorganisms, which participate in a variety of physiological functions. Intestinal dysbiosis is closely associated with the pathogenesis of several human diseases. Innate lymphoid cells (ILCs), which include NK cells, ILC1s, ILC2s, ILC3s and LTi cells, are a type of innate immune cells. They are enriched in the mucosal tissues of the body, and have recently received extensive attention. The gut microbiota and its metabolites play important roles in various intestinal mucosal diseases, such as inflammatory bowel disease (IBD), allergic disease, and cancer. Therefore, studies on ILCs and their interaction with the gut microbiota have great clinical significance owing to their potential for identifying pharmacotherapy targets for multiple related diseases. This review expounds on the progress in research on ILCs differentiation and development, the biological functions of the intestinal microbiota, and its interaction with ILCs in disease conditions in order to provide novel ideas for disease treatment in the future.

Functional Polymorphisms of the Arachidonic Acid Pathway Associate with Risks and Clinical Outcomes of Allergic Diseases

Introduction: The arachidonic acid (AA) pathway plays a crucial role in allergic inflammatory diseases; however, the functional roles of allergy-associated single nucleotide polymorphisms (SNPs) in this pathway remain incompletely illustrated. Methods: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). We performed population genotyping on n = 2,880 individuals from the SMCSGES cohort to assess the associations of SNPs in the AA pathway genes with asthma and allergic rhinitis (AR). Spirometry assessments were performed to identify associations between SNPs and lung function among n = 74 pediatric asthmatic patients from the same cohort. Allergy-associated SNPs were functionally characterized using in vitro promoter luciferase assay, along with DNA methylome and transcriptome data of n = 237 peripheral blood mononuclear cell (PBMC) samples collected from a subset of the SMCSGES cohort. Results: Genetic association analysis showed 5 tag-SNPs from 4 AA pathway genes were significantly associated with asthma (rs689466 at COX2, rs35744894 at hematopoietic PGD2 synthase (HPGDS), rs11097414 at HPGDS, rs7167 at CRTH2, and rs5758 at TBXA2R, p < 0.05), whereas 3 tag-SNPs from HPGDS (rs35744894, rs11097414, and rs11097411) and 2 tag-SNPs from PTGDR (rs8019916 and rs41312470) were significantly associated with AR (p < 0.05). The asthma-associated rs689466 regulates COX2 promoter activity and associates with COX2 mRNA expression in PBMC. The allergy-associated rs1344612 was significantly associated with poorer lung function, increased risks of asthma and AR, and increased HPGDS promoter activity. The allergy-associated rs8019916 regulates PTGDR promoter activity and DNA methylation levels of cg23022053 and cg18369034 in PBMC. The asthma-associated rs7167 affects CRTH2 expression by regulating the methylation level of cg19192256 in PBMC. Conclusions: The present study identified multiple allergy-associated SNPs that modulate the transcript expressions of key genes in the AA pathway. The development of a “personalized medicine” approach with consideration of genetic influences on the AA pathway may hopefully result in efficacious strategies to manage and treat allergic diseases.

MIR222HG attenuates macrophage M2 polarization and allergic inflammation in allergic rhinitis by targeting the miR146a-5p/TRAF6/NF-κB axis.

Although M2 macrophages are involved in the orchestration of type 2 inflammation in allergic diseases, the mechanisms underlying non-coding RNA (ncRNA)-mediated macrophage polarization in allergic rhinitis (AR) have not been systematically understood. Here, we identified long non-coding RNA (lncRNA) MIR222HG as a key regulator of macrophage polarization and revealed its role in AR. Consistent with our bioinformatic analysis of GSE165934 dataset derived from the Gene Expression Omnibus (GEO) database, lncRNA-MIR222HG and murine mir222hg were downregulated in our clinical samples and animal models of AR, respectively. Mir222hg was upregulated in M1 macrophages and downregulated in M2 macrophages. The allergen-ovalbumin facilitated polarization of RAW264.7 cells to the M2 phenotype, accompanied by the downregulation of mir222hg expression in a dose-dependent manner. Mir222hg facilitates macrophage M1 polarization and reverses M2 polarization caused by ovalbumin. Furthermore, mir222hg attenuates macrophage M2 polarization and allergic inflammation in the AR mouse model. Mechanistically, a series of gain- and loss-of-function experiments and rescue experiments were performed to verify the role of mir222hg as a ceRNA sponge that adsorbed miR146a-5p, upregulated Traf6, and activated the IKK/IκB/P65 pathway. Collectively, the data highlight the remarkable role of MIR222HG in the modulation of macrophage polarization and allergic inflammation, as well as its potential role as a novel AR biomarker or therapeutic target.

BLOC1S1: An Unexpected Regulator of Th2 Cell-driven Inflammatory Responses

Abstract BLOC1S1 is an adaptor protein that modulates endosome-lysosome function as a component of numerous multiprotein complexes. We postulated that its modulation in CD4 +T cells may help us uncover the role of endosome-lysosome biology in adaptive immunity. In primary CD4 +T cells BLOC1S1 cre-recombinase knockout resulted in the preferential induction of Th2 compared to Th1 and Th17 cytokine production following T cell receptor activation. As atopic dermatitis is an allergic inflammatory skin disease characterized by the production of the type 2 cytokines in the skin we evaluated the effect of CD4 +T cell BLOC1S1 KO vs controls in calcipotriol-induced atopic dermatitis in mice. The absence of BLOC1S1 exhibited exacerbated atopic dermatitis accompanied with significantly elevated plasma IgE, skin eosinophilia, elevated type 2 responses, and inflammatory pathology relative to wild-type mice. The transcription factor Gata-3 is expressed in Th2 but not Th1 cells and plays a critical role in Th2 differentiation and atopic dermatitis. BLOC1S1 deficient CD4 +T cells showed enhanced nuclear factor kB (NF-kB), Gata3 and LC3 positive autophagosomes. Inhibition of NF-kB activity prevented Gata-3 expression, LC3 positive autophagosomes and Th2 cytokine production in BLOC1S1 −/− CD4 +T cells. This mouse model will now give us a platform to explore the role of endo-lysosomal biology in Th2 polarization and activation. NHLBI Division of Intramural Research (MNS-ZIA-HL005102)

A survey‐based study on diagnosis and management of vernal keratoconjunctivitis

A survey‐based study on diagnosis and management of vernal keratoconjunctivitis

Contribution of survivin to the immune system, allergies and autoimmune diseases.

In addition to malignancies, survivin (a member of the apoptosis inhibitor family) has been implicated in the pathogenesis of inflammatory disorders, including autoimmune and allergic diseases. Survivin is constantly expressed in the proliferating hematopoietic progenitor cells, and it is re-expressed in the mature cells of the innate and adaptive immunity, upon activation. Survivin enhances the expression of co-stimulatory molecules and MHC class II molecules in dendritic cells, and promotes the lifespan of macrophages, neutrophils, and eosinophils, while suppressing natural killer (NK) cell activity. Survivin has been implicated in T cell maturation, T cell expansion, effector CD4+ T cell differentiation, maintenance of memory CD4+ T and CD8+ T cells, as well as antibody production. Upregulated expression of survivin was indicated in the T cells as well as various samples collected from allergic patients. Survivin can contribute to the pathogenesis of allergic diseases via the promotion of the Th2 polarization, promoting IL-4 expression, compromising activation-induced cell death (AICD) in Th2 cells, and preventing apoptosis of eosinophils, as well as, amplification of eosinophilia. Moreover, survivin can interfere with clonal deletion of autoreactive T and B cells, as well as suppress Treg cell development and activity supporting the development of autoimmune diseases. This review discusses the role of survivin in immunity, allergy and autoimmunity as well as provides evidence that survivin may be considered as a novel therapeutic target for the treatment of allergic and autoimmune diseases.

Activation of Mast Cells by Neuropeptides: The Role of Pro-Inflammatory and Anti-Inflammatory Cytokines.

Mast cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in the scientific literature; it is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptide substance P (SP), corticotropin-releasing hormone (CRH), and neurotensin, and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

The epithelial barrier theory: Development and exacerbation of allergic and other chronic inflammatory diseases.

It is now longer than half a century, humans, animals, and nature of the world are under the influence of exposure to many newly introduced noxious substances. These exposures are nowadays pushing the borders to be considered as the causative or exacerbating factors for many chronic disorders including allergic, autoimmune/inflammatory, and metabolic diseases. The epithelial linings serve as the outermost body's primary physical, chemical, and immunological barriers against external stimuli. The "epithelial barrier theory" hypothesizes that these diseases are aggravated by an ongoing periepithelial inflammation triggered by exposure to a wide range of epithelial barrier-damaging insults that lead to "epithelitis" and the release of alarmins. A leaky epithelial barrier enables the microbiome's translocation from the periphery to interepithelial and even deeper subepithelial areas together with allergens, toxins, and pollutants. Thereafter, microbial dysbiosis, characterized by colonization of opportunistic pathogen bacteria and loss of the number and biodiversity of commensal bacteria take place. Local inflammation, impaired tissue regeneration, and remodeling characterize the disease. The infiltration of inflammatory cells to affected tissues shows an effort to expulse the tissue invading bacteria, allergens, toxins, and pollutants away from the deep tissues to the surface, representing the "expulsion response." Cells that migrate to other organs from the inflammatory foci may play roles in the exacerbation of various inflammatory diseases in distant organs. The purpose of this review is to highlight and appraise recent opinions and findings on epithelial physiology and its role in the pathogenesis of chronic diseases in view of the epithelial barrier theory.

Altered phosphatidylcholine metabolism in children with atopic dermatitis

Disturbances in circulating phospholipids levels and their association with the phenotype have been observed in inflammatory disorders and allergic diseases, such as asthma. However, the role and related mechanisms of metabolites in the development of AD are rarely known. We sought to apply serum untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in children with AD.

Disease trends after Helicobacter pylori eradication based on Japanese nationwide claims and the health check-up database.

Helicobacter pylori (H. pylori) infection is a risk factor for many diseases, including peptic ulcer disease and gastric cancer. While H. pylori eradication therapy can prevent these diseases, potentially unfavorable effects of eradication therapy have also been reported in some diseases, such as gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), inflammatory bowel disease (IBD), allergic diseases, and metabolic diseases. Consequently, both positive and negative impacts should be considered when assessing the effects of H. pylori eradication therapy. To compare the incidence of these diseases before and after H. pylori eradication and to comprehensively assess its effects. This retrospective cohort study used a Japanese nationwide health claims database (April 2009-March 2020), developed by the Japanese Ministry of Health, Labour and Welfare. The database contained almost all health insurance claims data issued in Japan, and specific health check-up data for individuals who took the check-ups. Descriptive statistics were used for the analyses. Patients who received primary eradication therapy were defined as those prescribed medi-cation for H. pylori eradication. New diagnoses, defined as incidence of upper gastrointestinal diseases and IBD, and prevalence of allergic diseases were compared before and after eradication. The incidence and prevalence of each disease were also compared between the 3-year period before eradication (from the 4th to the 2nd year prior to the year of eradication) and the 3-year period after eradication (from the 1st to the 3rd year after the year of eradication) based on the age category and calendar year and month. Changes in body mass index and proportion of patients with metabolic syndrome (MS) were examined before and after eradication. We identified 5219731 patients who received primary eradication therapy. The 65-69 years age group had the greatest number of patients in both sexes. There was no significant increase in the incidence of GERD after eradication when considering the effects of aging and reporting period. However, the incidence of BE was higher in the 3-year period after eradication than in the 3-year period before eradication for all age categories (0.02%-0.10% vs < 0.01%-0.05%). The incidence of IBD and prevalence of allergic disease were also higher after eradication. In contrast, the incidence of gastric and duodenal ulcers and gastritis was reduced after eradication. In patients with at least one entry of health check-up data (1701111 patients), the percentage of patients with MS showed a slight increase following eradication (11.0% in the year of eradication and 12.2% after 5 years). The results suggest that H. pylori eradication therapy reduces peptic ulcers and gastritis; however, it is associated with increased incidence of several other chronic diseases.

Prinsepia utilis Royle leaf extract: Ameliorative effects on allergic inflammation and skin lesions in allergic contact dermatitis and polyphenolic profiling through UPLC–MS/MS coupled to chemometric analysis

Ethnopharmacological relevanceAllergic contact dermatitis (ACD) is a common allergic inflammatory disease that is concomitant with skin swelling, redness, dry itching, and relapses. Prinsepia utilis Royle, a Chinese and Indian folk medicine, is rich in polyphenols with potential anti-inflammatory and skin-protective activities. However, the underlying mechanism of P. utilis leaf (PUL) in the treatment of ACD and its functional basis remains unclear. Aim of the studyThis study is aimed to explore and reveal the active substances and mechanism of PUL against ACD. Materials and methodsHyaluronidase inhibitory assay and fluorescein isothiocyanate (FITC)-induced ACD mouse model were performed to assess the antiallergic effects of PUL in vitro and in vivo. Different solvents were applied to obtain multiple PUL extracts. The extracts were further tested for total phenolic content (TPC) and total flavonoid content (TFC) by using spectrophotometric assays. Polyphenolic profiles were analyzed by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), and a simultaneous quantification method was established using UPLC-QTrap-MS/MS through multiple reaction monitoring (MRM) and applied to analyze the pharmacokinetics of the multiple major polyphenols of PUL in mice. ResultsThe water extract of PUL with the highest TPC/TFC exhibited the strongest antihyaluronidase effect (IC50 = 231.93 μg/mL). In vivo assays indicated that the oral administration of PUL water extract dose-dependently attenuated ACD-like symptoms by decreased interleukin (IL)-4, IL-5, IL-13, IL-33, thymic stromal lymphopoietin, and IgE production, suppressed eosinophil and basophil secretion, and increasing the expression of tight junction (TJ) proteins (claudin-1 [CLDN-1] and occludin). Concomitantly, UPLC–QTOF–MS/MS analysis enabled the identification of 60 polyphenols and the pharmacokinetic parameters of seven quantified constituents of PUL were characterized. Four compounds, trans-p-coumaric acid 4-O-β-D-glucopyranoside (11), vicenin-2 (21), isoschaftoside (31), and kaempferol 3-O-(2″,6″-di-O-α-L-rhamnopyransoyl)-β-D-glucopyranoside (38) which displayed satisfactory pharmacokinetic features, were considered as potential effective substances in PUL. ConclusionsPUL water extract ameliorated the allergic inflammation of ACD by repairing the epithelial barrier and alleviating Th2-type allergic inflammation. The anti-allergic effect of PUL is closely related to its phenolic substances, and compounds 11, 21, 31, and 38 were the active substances of PUL. It revealed that P. utilis could be developed as a new source of antiallergic agents for ACD therapy.

Pregnancy Outcomes in Females with Eosinophilic Esophagitis: A Nationwide Population-Based Study

Introduction: Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. It has a peak incidence in the 2nd and 3rd decades of life. Despite this, little is known about pregnancy outcomes in patients with EoE. Methods: Using a validated histopathologic and nationwide population-based cohort for the diagnosis of EoE, we examined maternal and fetal outcomes, with preterm birth as the primary outcome, in females with EoE compared to matched controls. Odds ratios (ORs) were calculated using logistic regression. Results: Between 1992 and 2016, we identified 19 females with EoE who gave birth to 23 children (reference births: n = 115). There was 1 (4.3%) preterm birth in the EoE cohort versus 8 (7.0%) in the reference cohort (OR = 0.60; 95% CI = 0.07–5.14). Secondary fetal outcomes included stillbirth, neonatal death, small for gestational age, low birth weight (LBW), and low Apgar score. Of these, LBW (<2,500 g) in patients with EoE compared to controls correlated to an OR of 12.42 (95% CI = 1.26–122.42); however, this finding was based on very low numbers. The remaining fetal outcomes were not significantly different between females with EoE and controls. Secondary pregnancy and maternal outcomes including induction of labor, instrumental delivery, gestational diabetes, or pre-eclampsia were not significantly different between patients with EoE and controls. Discussion/Conclusion: Overall in this nationwide cohort study, we did not find increased association of preterm birth in patients with EoE.

Intranasal administration of nucleus-deliverable GATA3-TMD alleviates the symptoms of allergic asthma

Although the T helper 2 (Th2) subset is a critical player in the humoral immune response to extracellular parasites and suppression of Th1-mediated inflammation, Th2 cells have been implicated in allergic inflammatory diseases such as asthma, allergic rhinitis, and atopic dermatitis. GATA binding protein 3 (GATA3) is a primary transcription factor that mediates Th2 differentiation and secretion of Th2 cytokines, including IL-4, IL-5, and IL-13. Here, a nucleus-deliverable form of GATA3-transcription modulation domain (TMD) (ndG3-TMD) was generated using Hph-1 human protein transduction domain (PTD) to modulate the transcriptional function of endogenous GATA3 without genetic manipulation. ndG3-TMD was shown to be efficiently delivered into the cell nucleus quickly without affecting cell viability or intracellular signaling events for T cell activation. ndG3-TMD exhibited a specific inhibitory function for the endogenous GATA3-mediated transcription, such as Th2 cell differentiation and Th2-type cytokine production. Intranasal administration of ndG3-TMD significantly alleviated airway hyperresponsiveness, infiltration of immune cells, and serum IgE level in an OVA-induced mouse model of asthma. Also, Th2 cytokine secretion by the splenocytes isolated from the ndG3-TMD-treated mice substantially decreased. Our results suggest that ndG3-TMD can be a new therapeutic reagent to suppress Th2-mediated allergic diseases through intranasal delivery.