PRO-INFLAMMATORY CYTOKINES IL-4 AND IL-13 IN CHILDREN WITH "SECRETOR" AND "NON-SECRETOR" STATUS OF H ANTIGEN DURING FOOD ALLERGY

Analysis of peculiarities of production of inflammatory cytokines IL-4 and IL-13 in children with approved diagnosis "food allergy" with "secretor" and "non-secretor" H-antigen status was carried out. "Non-secretor" children were shown to have 1.7 times higher content of a Th2 inflammation marker, IL-4, in blood serum than children with "secretor" status. IL-13 content was also elevated, although not so significantly. In children with "non-secretor" status, higher level of pro-inflammatory cytokines correlated with more severe progression of allergic inflammation, which makes determination of H antigen in the saliva of children and their mothers a promising non-invasive prognostic marker of progression of allergic inflammation in children with food allergy.

Positionspapier: Empfehlungen zur Anwendung von Omalizumab bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem – Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC)

Zusammenfassung Hintergrund Die chronische Rhinosinusitis mit Nasenpolypen (CRSwNP) ist eine multifaktorielle entzündliche Erkrankung der paranasalen Schleimhäute, der als Endotyp meistens eine TH2-Inflammation zugrunde liegt. IgE-Antikörper spielen dabei eine wichtige Rolle. Der anti-IgE-Antikörper Omalizumab wurde im August 2020 für die Therapie der schweren CRSwNP zugelassen. Methoden In einer Literatursuche wurde die Immunologie der CRSwNP analysiert und die Evidenz zur Wirkung von Omalizumab bei dieser Erkrankung ermittelt durch Recherchen in Medline, Pubmed sowie den nationalen und internationalen Studien- und Leitlinien-Registern und der Cochrane Library. Ergebnisse Basierend auf diesen Angaben aus der internationalen Literatur werden von einem Expertengremium Empfehlungen für die Anwendung von Omalizumab bei CRSwNP im deutschen Gesundheitssystem gegeben. Schlussfolgerung Omalizumab ist zugelassen für Patienten ab 18 Jahren mit schwerer chronischer Rhinosinusitis mit Nasenpolypen als Zusatztherapie zu intranasalen Kortikosteroiden (INCS), wenn durch eine Therapie mit INCS keine ausreichende Krankheitskontrolle erzielt werden kann.

Psoriasis in an Asian patient with atopic dermatitis treated with dupilumab

Dupilumab is a monoclonal antibody against the alpha subunit of the interleukin (IL)-4 receptor that inhibits IL-4 and IL-13 signaling, which plays a central role in Th2 inflammation in AD.Here, we report the first Asian case of psoriasis unexpectedly induced by dupilumab therapy for AD. Compared with European and American AD phenotype, Asian AD phenotype is characterized by changes in the psoriasiform phenotype, associating with higher Th17 activation. The blockade of IL-4/IL-13 signaling by dupilumab may induce psoriasis eruption corresponding to shift from a Th2- to Th17- mediated inflammatory response in the skin.

Electronic Cigarettes and Asthma: What Do We Know So Far?

Electronic cigarettes (EC) are a novel product, marketed as an alternative to tobacco cigarette. Its effects on human health have not been investigated widely yet, especially in specific populations such as patients with asthma. With this review, we use the existing literature in order to answer four crucial questions concerning: (1) ECs’ role in the pathogenesis of asthma; (2) ECs’ effects on lung function and airway inflammation in patients with asthma; (3) ECs’ effects on asthma clinical characteristics in asthmatics who use it regularly; and (4) ECs’ effectiveness as a smoking cessation tool in these patients. Evidence suggests that many EC compounds might contribute to the pathogenesis of asthma. Lung function seems to deteriorate by the use of EC in this population, while airway inflammation alters, with the aggravation of T-helper-type-2 (Th2) inflammation being the most prominent but not the exclusive effect. EC also seems to worsen asthma symptoms and the rate and severity of exacerbations in asthmatics who are current vapers, whilst evidence suggests that its effectiveness as a smoking cessation tool might be limited. Asthmatic patients should avoid using EC.

CBX4 regulates long-form thymic stromal lymphopoietin-mediated airway inflammation through SUMOylation in HDM-induced asthma

Rationale: Thymic stromal lymphopoietin (TSLP) is present in two distinct isoforms, short-form (sfTSLP) and long-form (lfTSLP). lfTSLP promotes inflammation while sfTSLP inhibits inflammation in allergic asthma. However, little is known about the regulation of lfTSLP and sfTSLP during allergic attack in asthma airway epithelium. Methods and Results: Here, we report that SUMOylation was enhanced in HDM-induced allergic asthma airway epithelium. Inhibition of SUMOylation significantly alleviated airway Th2 inflammation and lfTSLP expression. Mechanistically, CBX4, a SUMOylation E3 ligase, enhanced lfTSLP, but not sfTSLP, mRNA translation through the RNA binding protein, MEX-3B. MEX-3B promoted lfTSLP translation through binding of its KH domains to the lfTSLP mRNA. Furthermore, CBX4 regulated MEX-3B transcription in HBE through enhancing SUMOylation levels of the transcription factor, TFII-I. Conclusion: We demonstrate an important mechanism whereby CBX4 promotes MEX-3B transcription through enhancing TFII-I SUMOylation, and MEX-3B enhances the expression of lfTSLP through binding to the lfTSLP mRNA and promoting its translation. Our findings uncover a novel target of CBX4 for therapeutic agents to lfTSLP-mediated asthma.

Translational Relevance of Mouse Models of Atopic Dermatitis

The complexity of atopic dermatitis (AD) continues to present a challenge in the appropriate selection of a mouse model because no single murine model completely recapitulates all aspects of human AD. This has been further complicated by recent evidence of the distinct AD endotypes that are dictated by unique patterns of inflammation involving Th1, Th2, Th17, and Th22 axes. A review of currently used mouse models demonstrates that while all AD mouse models consistently exhibit Th2 inflammation, only some demonstrate concomitant Th17 and/or Th22 induction. As the current understanding of the pathogenic contributions of these unique endotypes and their potential therapeutic roles expands, ongoing efforts to maximize a given mouse model’s homology with human AD necessitates a close evaluation of its distinct immunological signature.

The Anti-asthmatic Effect of Intratracheally Treated Mesenchymal Stem Cells via Modulation of Lung Macrophage Activation

BackgroundMesenchymal stem cells (MSCs) possess immunomodulatory properties that provide therapeutic potential for the treatment of inflammatory diseases. While the therapeutic and clinical effects of MSCs are partially known, the effects of its administration to the airway in asthma, a chronic airway inflammatory disease, remain unclear.MethodsSix-week-old female BALB/c mice were sensitized and challenged with ovalbumin. The effects of intratracheally administered umbilical cord MSCs were evaluated by measuring airway hyperresponsiveness, airway inflammatory cell analysis, histological analysis, flow cytometry, and quantitative real-time PCR. Furthermore, ex vivo experiments confirmed the effect of MSC treatment on macrophages that originated from bronchoalveolar lavage fluid and were treated with interleukin (IL)-4 to induce M2 activation. Additionally, an in vitro transwell assay confirmed the effect of MSCs on macrophage activation through direct or indirect treatment using the CRL-2019 alveolar macrophage (AM) cell line.ResultsIntratracheal administration of MSCs significantly decreased the elevated levels of inflammatory cells and airway resistance in the murine asthma model. MSC administration also significantly decreased the numbers of Th2 cells, ILC2, and macrophages in the lungs of asthmatic mice. In particular, MHCII and CD86 expression was prominently reduced in dendritic cells and AMs following MSC treatment. Suppressed SiglecF+CD11c+CD11b- resident AMs, presenting strong negative correlation with type II inflammatory cells such as Th2 cells, ILC2, and eosinophils, were restored by intratracheal MSC treatment. Typical macrophage polarization to M2, particularly M2a, was significantly diminished. Expression levels of markers presenting M2 polarization and Th2 inflammation were decreased in the asthma model upon MSC administration. Ex vivo experiments of IL-4 treated AMs confirmed that MSC treatment reduced Il-12 and Tnfa expression as well as that of M2 markers such as Cd206 and Retnla. In vitro experiments of IL-4 treated AMs confirmed that both direct and indirect MSC treatments through transwells significantly reduced Il-5 and Il-13 expression. No difference between the two treatment methods was found.ConclusionsUmbilical cord MSCs appear to regulate pulmonary macrophages, suppress Th2 inflammation, and mediate anti-asthmatic effects via soluble mediators.

Role of periostin in ECRS

Periostin, an extracelluar matrix protein belonging to the fasciclin family, has been reported to play a key role in the process of Th2-inflammation disease. As eoshinophilic chronic rhinosinusitis has a higher incident rate, studies show that periostin has participated in the process of inflammation and remodeling. This review mainly to summarize researches of periostin in ECRS and to investigate the clinical significance and expression of periostin.