Osthole alleviates food allergy by blocking IL-33/ST2 pathway and targeting ILC2-CD4+T response

Osthole is widely used in medicine because of its anti-oxidative, anti-allergenic and anti-inflammatory. In this study, we explored the protective effects of osthole on food allergenic mice and investigated its potential mechanism of action. We first established a food allergic mouse model by intraperitoneal sensitization and OVA (ovalbumin) oral challenge. Osthole were orally administered before OVA challenge. Diarrhea and allergy scores were used to assess food allergy symptoms. The pathological changes of the intestine were examined by H&E staining and electron microscopy. OVA-IgE, mucosal mast cell protease-1 (mMCP-1), IL-33, ST2, group 2 innate lymphoid cell (ILC2), and regulatory T (Treg) related-cytokine levels were assessed.We found that the oral administration of osthole after OVA sensitization could improve food allergy symptoms and induce beneficial intestinal pathological changes in mice. Osthole reduce the levels of IgE and mMCP-1 and inhibited the IL33/ST2 signaling pathway, thereby blocking ILC2 response and improving Treg response

Molecular mechanism of interleukin-17A regulating airway epithelial cell ferroptosis based on allergic asthma airway inflammation

Interleukin-17A (IL-17A) levels are elevated in patients with asthma. Ferroptosis has been identified as the non-apoptotic cell death type associated with asthma. Data regarding the relation of ferroptosis with asthma and the effect of IL-17A on modulating ferroptosis in asthma remain largely unclear. The present work focused on investigating the role of IL-17A in allergic asthma-related ferroptosis and its associated molecular mechanisms using public datasets, clinical samples, human bronchial epithelial cells, and an allergic asthma mouse model. We found that IL-17A was significantly upregulated within serum in asthma cases. Adding IL-17A significantly increased ferroptosis within human bronchial epithelial cells (BEAS-2B). In ovalbumin (OVA)-induced allergic asthmatic mice, IL-17A regulated and activated lipid peroxidation induced ferroptosis, whereas IL-17A knockdown effectively inhibited ferroptosis in vivo by protection of airway epithelial cells via the xCT-GSH-GPX4 antioxidant system and reduced airway inflammation. Mouse mRNA sequencing results indicated that the tumor necrosis factor (TNF) pathway was the differential KEGG pathway in the OVA group compared to healthy controls and the OVA group compared to the IL-17A knockout OVA group. We further used N-acetylcysteine (TNF inhibitor) to inhibit the TNF signaling pathway, which was found to protect BEAS-2B cells from IL-17A induced lipid peroxidation and ferroptosis damage. Our findings reveal a novel mechanism for the suppression of ferroptosis in airway epithelial cells, which may represent a new strategy for the use of IL-17A inhibitors against allergic asthma

DataSheet_1_Allergen immunotherapy combined with Notch pathway inhibitors improves HDM-induced allergic airway inflammation and inhibits ILC2 activation.docx

IntroductionGroup 2 innate lymphoid cells (ILC2s) play a crucial role in house dust mite (HDM)-induced allergic inflammation, and allergen immunotherapy (AIT) holds promise for treating the disease by reducing the frequency of ILC2s. Despite significant progress in AIT for allergic diseases, there remains a need to improve the control of allergic symptoms.MethodsWe investigated the synergistic effect of the Notch signaling pathway and subcutaneous immunotherapy (SCIT) in treating allergic airway inflammation in mice and their impact on the ratio of ILC2s in lung tissues. This was achieved by establishing the HDM-induced airway allergic disorders (HAAD) model and SCIT model. Additionally, we conducted in vitro investigations into the effect of the Notch signaling pathway on the secretory function of activated ILC2s using fluorescence-activated cell sorting. Furthermore, we explored the coactivation of the Notch signaling pathway with SCIT in vitro by sorting ILC2s from the lung tissues of mice after SCIT modeling.ResultsPreviously, our group demonstrated that Notch signaling pathway inhibitors can reduce allergic airway inflammation in mice. Notch signaling induces lineage plasticity of mature ILC2s. In this study, we showed that AIT alleviates allergic airway inflammation and suppresses the frequency of ILC2s induced by HDM. Interestingly, AIT combined with a γ-secretase inhibitor (GSI), an inhibitor of the Notch signaling pathway, significantly inhibited the frequency of ILC2s, reduced airway inflammation, and suppressed Th2-type responses in a mouse model. Furthermore, lung ILC2s from HDM-challenged mice with or without AIT were treated with GSI in vitro, and we found that GSI dramatically reduced the secretion of type 2 inflammatory factors in ILC2s.DiscussionThese findings suggest that Notch signaling pathway inhibitors can be used as adjuvant therapy for AIT and may hold potential treatment value in the cooperative control of allergic airway inflammation during early AIT.</p

Measurement of inclusive and differential cross sections of single top quark production in association with a W boson in proton-proton collisions at s\sqrt{s} = 13.6 TeV

International audienceThe first measurement of the inclusive and normalised differential cross sections of single top quark production in association with a W boson in proton-proton collisions at a centre-of-mass energy of 13.6 TeV is presented. The data were recorded with the CMS detector at the LHC in 2022, and correspond to an integrated luminosity of 34.7 fb$^{-1}$. The analysed events contain one muon and one electron in the final state. For the inclusive measurement, multivariate discriminants exploiting the kinematic properties of the events are used to separate the signal from the dominant top quark-antiquark production background. A cross section of 82.3 $\pm$ 2.1 (stat) ${}^{+9.9}_{-9.7}$ (syst) $\pm$ 3.3 (lumi) pb is obtained, consistent with the predictions of the standard model. A fiducial region is defined according to the detector acceptance to perform the differential measurements. The resulting differential distributions are unfolded to particle level and show good agreement with the predictions at next-to-leading order in perturbative quantum chromodynamics

Search for long-lived heavy neutral leptons in proton-proton collision events with a lepton-jet pair associated with a secondary vertex at s\sqrt{s} = 13 TeV

International audienceA search for long-lived heavy neutral leptons (HNLs) using proton-proton collision data corresponding to an integrated luminosity of 138 fb$^{-1}$ collected at $\sqrt{s}$ = 13 TeV with the CMS detector at the CERN LHC is presented. Events are selected with a charged lepton originating from the primary vertex associated with the proton-proton interaction, as well as a second charged lepton and a hadronic jet associated with a secondary vertex that corresponds to the semileptonic decay of a long-lived HNL. No excess of events above the standard model expectation is observed. Exclusion limits at 95% confidence level are evaluated for HNLs that mix with electron and/or muon neutrinos. Limits are presented in the mass range of 1-16.5 GeV, with excluded square mixing parameter values reaching as low as 2 $\times$ 10$^{-7}$. For masses above 11 GeV, the presented limits exceed all previous results in the semileptonic decay channel, and for some of the considered scenarios are the strongest to date

Study of WH production through vector boson scattering and extraction of the relative sign of the W and Z couplings to the Higgs boson in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for the production of a W boson and a Higgs boson through vector boson scattering (VBS) is presented, using CMS data from proton-proton collisions at $\sqrt{s}$ = 13 TeV collected from 2016 to 2018. The integrated luminosity of the data sample is 138 fb$^{-1}$. Selected events must be consistent with the presence of two jets originating from VBS, the leptonic decay of the W boson to an electron or muon, and a Higgs boson decaying into a pair of b quarks, reconstructed as either a single merged jet or two resolved jets. A measurement of the process as predicted by the standard model (SM) is performed alongside a study of beyond-the-SM (BSM) scenarios. The SM analysis sets an observed (expected) 95% confidence level upper limit of 14.3 (9.0) on the ratio of the measured VBS WH cross section to that expected by the SM. The BSM analysis, conducted within the so-called $\kappa$ framework, excludes all scenarios with $\lambda_\mathrm{WZ}$ $\lt$ 0 that are consistent with current measurements, where $\lambda_\mathrm{WZ}$ = $\kappa_\mathrm{W}/\kappa_\mathrm{Z}$ and $\kappa_\mathrm{W}$ and $\kappa_\mathrm{Z}$ are the HWW and HZZ coupling modifiers, respectively. The signficance of the exclusion is beyond 5 standard deviations, and it is consistent with the SM expectation of $\lambda_\mathrm{WZ}$ = 1

The CMS statistical analysis and combination tool: COMBINE

This paper describes the COMBINE software package used for statistical analyses by the CMS Collaboration. The package, originally designed to perform searches for a Higgs boson and the combined analysis of those searches, has evolved to become the statistical analysis tool presently used in the majority of measurements and searches performed by the CMS Collaboration. It is not specific to the CMS experiment, and this paper is intended to serve as a reference for users outside of the CMS Collaboration, providing an outline of the most salient features and capabilities. Readers are provided with the possibility to run COMBINE and reproduce examples provided in this paper using a publicly available container image. Since the package is constantly evolving to meet the demands of ever-increasing data sets and analysis sophistication, this paper cannot cover all details of COMBINE. However, the online documentation referenced within this paper provides an up-to-date and complete user guide

Searches for Higgs boson production through decays of heavy resonances

The discovery of the Higgs boson has led to new possible signatures for heavy resonance searches at the LHC. Since then, search channels including at least one Higgs boson plus another particle have formed an important part of the program of new physics searches. In this report, the status of these searches by the CMS Collaboration is reviewed. Searches are discussed for resonances decaying to two Higgs bosons, a Higgs and a vector boson, or a Higgs boson and another new resonance, with proton-proton collision data collected at $\sqrt{s}$ = 13 TeV in the years 2016-2018. A combination of the results of these searches is presented together with constraints on different beyond-the-standard model scenarios, including scenarios with extended Higgs sectors, heavy vector bosons and extra dimensions. Studies are shown for the first time by CMS on the validity of the narrow-width approximation in searches for the resonant production of a pair of Higgs bosons. The potential for a discovery at the High Luminosity LHC is also discussed

Searches for Higgs boson production through decays of heavy resonances

The discovery of the Higgs boson has led to new possible signatures for heavy resonance searches at the LHC. Since then, search channels including at least one Higgs boson plus another particle have formed an important part of the program of new physics searches. In this report, the status of these searches by the CMS Collaboration is reviewed. Searches are discussed for resonances decaying to two Higgs bosons, a Higgs and a vector boson, or a Higgs boson and another new resonance, with proton-proton collision data collected at $\sqrt{s}=$ 13 TeV in the years 2016-2018. A combination of the results of these searches is presented together with constraints on different beyond-the-standard model scenarios, including scenarios with extended Higgs sectors, heavy vector bosons and extra dimensions. Studies are shown for the first time by CMS on the validity of the narrow-width approximation in searches for the resonant production of a pair of Higgs bosons. The potential for a discovery at the High Luminosity LHC is also discussed.The discovery of the Higgs boson has led to new possible signatures for heavy resonance searches at the LHC. Since then, search channels including at least one Higgs boson plus another particle have formed an important part of the program of new physics searches. In this report, the status of these searches by the CMS Collaboration is reviewed. Searches are discussed for resonances decaying to two Higgs bosons, a Higgs and a vector boson, or a Higgs boson and another new resonance, with proton-proton collision data collected at $\sqrt{s}$ = 13 TeV in the years 2016-2018. A combination of the results of these searches is presented together with constraints on different beyond-the-standard model scenarios, including scenarios with extended Higgs sectors, heavy vector bosons and extra dimensions. Studies are shown for the first time by CMS on the validity of the narrow-width approximation in searches for the resonant production of a pair of Higgs bosons. The potential for a discovery at the High Luminosity LHC is also discussed