FcεRI signaling in the modulation of allergic response: role of mast cell-derived exosomes

Mast cells (MCs) are immune cells that act as environment resident sentinels playing a crucial role in Th2-mediated immune responses, including allergic reactions. Distinguishing features of MCs are the presence of numerous cytoplasmic granules that encapsulate a wide array of preformed bio-active molecules and the constitutive expression of the high affinity receptor of IgE (Fc epsilon RI). Upon Fc epsilon RI engagement by means of IgE and multivalent antigens, aggregated receptors trigger biochemical pathways that ultimately lead to the release of granule-stored and newly synthesized pro-inflammatory mediators. Additionally, MCs are also able to release exosomes either constitutively or upon stimulation. Exosomes are nanosized vesicles of endocytic origin endowed with important immunoregulatory properties, and represent an additional way of intercellular communication. Interestingly, exosomes generated upon Fc epsilon RI engagement contain co-stimulatory and adhesion molecules, lipid mediators, and MC-specific proteases, as well as receptor subunits together with IgE and antigens. These findings support the notion that Fc epsilon RI signaling plays an important role in influencing the composition and functions of exosomes derived by MCs depending on their activation status

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Mast cell-derived nanovesicles potentiate allergic inflammation

Mast cells (MCs) play a major role in allergic diseases: After activation by the high affinity receptor for IgE (FcepsilonRI), they release a high number of pro-inflammatory factors. Moreover, MCs can also produce exosomes, nanosized vesicles that might act as vehicles for intercellular communication. However, evidence of a role for MC-derived exosomes during allergic inflammation is limited. The aim of my PhD project was to characterize exosome-like vesicles released by unstimulated and IgE-stimulated MCs. Secreted nanovesicles were purified from the supernatant of MCs and from human sera by a series of centrifugations and ultracentrifugations and, in order to assess their purity, they were characterized in terms of morphology, size and marker expression. The presence of FcepsilonRI/IgE complexes was evaluated by western blotting combined with FACS analysis and ELISA. MC activation was measured by degranulation assay and multiplex immune-assay, and exosome uptake was analysed by confocal microscopy and flow cytometry. We found that FcepsilonRI engagement increases the amount of exosome release compared to the constitutive production. Moreover, only exosomes secreted upon antigen stimulation display both surface IgE and antigen. We have also demonstrated that vesicles exposing IgE and antigen are efficiently internalized by sensitized MCs and are able to induce their degranulation as well as pro-inflammatory cytokine production. Finally, we found that exosomes purified from serum of atopic patients are also endowed with FcepsilonRI/IgE complexes. All together, these findings reveal a potential novel mechanism of allergic reaction amplification

Endocitosi del recettore ad alta affinità per le IgE sui mastociti: conseguenze funzionali

I mastociti sono i principali mediatori cellulari delle risposte immunitarie mediate da IgE che includono le reazioni allergiche e alcune risposte protettive ai parassiti. I mastociti sono localizzati in siti anatomici strategici (in prossimità dei vasi del microcircolo a livello di cute e mucose) e in seguito alla loro attivazione, promossa dall’aggregazione del recettore ad alta affinità per le IgE (FcεRI), partecipano alla risposta immunitaria innata e regolano quella acquisita mediante il rilascio di mediatori proinfiammatori preformati e di nuova sintesi. I meccanismi molecolari responsabili dell’attivazione funzionale dei mastociti sono contro- bilanciati da una serie altrettanto complessa e sofisticata di meccanismi inibitori. Uno dei meccanismi deputati allo spegnimento della risposta, prevede la rimozione dei complessi recettoriali aggregati dalla superficie cellulare mediante endocitosi clatrina- e ubiquitina-dipendente. Questo articolo fornisce una panoramica dei principali adattatori molecolari ed enzimi che contribuiscono a modulare la risposta immunitaria IgE dipendente perchè direttamente im- plicati nell'endocitosi del recettore FcεRI, ma anche perchè coinvolti nel rilascio dei comples- si recettoriali aggregati in nanovescicole secrete dai mastociti, gli esosomi

Tdap Booster Vaccination for Adults: Real-World Adherence to Current Recommendations in Italy and Evaluation of Two Alternative Strategies

Background: While the effectiveness of tetanus-diphtheria-pertussis childhood immunization programs is unquestionable, the actual need for a periodic boosting vaccination in adults is controversial. In Italy, the Ministry of Health recommends a Tdap booster vaccination every 10 years. The aim of this study is to assess the real-world adherence of Italian regional healthcare services to national recommendations and to evaluate two alternative strategies. Methods: Annual Tdap vaccine requirements by the 21 Italian regions were retrieved from related tender announcements, and regional and national vaccination coverage rates (VCRs) were estimated for three scenarios, namely the currently recommended 10-year booster vaccination, a single booster shot at age 50 and at age 65. Results: In Scenario 1, no region reached a VCR > 30%, and the national VCR was 10.6%; in Scenario 2, five regions achieved the optimal vaccination coverage of ≥95%, but the vast majority continued to have inadequate VCRs, with a national VCR of 54.4%; in Scenario 3, five regions reached VCRs exceeding 100%, with VCRs from other regions significantly improving and a national VCR of 74.8%. Conclusions: A substantial lack of adherence by Italian regional healthcare services to current national recommendations on tetanus-diphtheria-pertussis adult vaccination was shown. Scenario 3 is the most feasible, i.e., a single booster shot at age 65, possibly administrable along with other already-recommended, age-specific vaccines

Active noise within the generating/pumping groups of a large hydroelectric plant

This work is related to a feasibility study for the implementation of an active noise control system to reduce the hydraulic turbomachine's noise in the Presenzano power plant. Previous studies showed that interested turbines are low frequencies noise sources, generating pure tones at 150 and 200 Hz (third and fourth harmonics of the turbine's BPF). At these frequencies passive noise control systems are ineffective in front of relevant costs and an active approach was so decided to be tested. In accordance with a classical ..

Menzione d'onore XXVII Compasso d'Oro - AIS/Design Journal. Storia e ricerche, V. 7 N. 12-13 (2020): Social Design. Design e “bene comune”

La rivista, online e open-access, l’unica rivista scientifica esclusivamente dedicata alla storia del design italiano e internazionale, ha dedicato un numero monografico a “Social Design. Design e bene comune”. Affronta dal punto di vista storico un argomento vivo nelle pratiche attuali del design e oggetto di studi e teorizzazioni, che però non è stato mai approfondito attraverso ricerche storiche puntuali. Dai saggi presentati nel numero della rivista emerge come questo ambito abbia solide radici nella seconda metà del Novecento e come il design italiano abbia dato propri e significativi contributi sia in termini di pensiero teorico, critico e metodologico, sia dal punto di vista progettuale e di buone pratiche