SummaryEnterocytes used to be studied particularly in terms of digestion protagonists. However, as the immune functions of the intestinal tract were better understood, it became clear that enterocytes are not mere bystanders concerning the induction of immune tolerance to dietary peptides and gut microbiota. In fact, enterocytes are involved actively in shaping the intestinal immune environment, designed for maintaining a non-belligerent state. This tolerant milieu of the gut immune system is achieved by keeping a balance between suppression and stimulation of the inflammatory responses. Our review presents the current state of knowledge concerning the relationship between enterocytes and immune cells (dendritic cells, lymphocytes), with emphasis on the enterocytes' impact on the mechanisms leading to the induction of oral tolerance.

Background Asthma is a chronic airway disease affecting millions of people. Better methods to define asthma subgroups using clinical parameters and molecular biomarkers are crucial in the development of personalized medicine. Objective The aim of this study was to determine if circulating microRNAs (miRNAs) may be used to distinguish well–defined asthma groups. Methods Blood serum from 116 well-defined subjects, including healthy controls and individuals with allergic or non-allergic asthma, from the West Sweden Asthma Study were included. Serum was analyzed for circulating miRNA expression of miR-126, − 145, −146a, − 155, − 223, and -374a and eosinophil cationic protein (ECP). Correlations between clinical characteristics and circulating miRNA expression as well as potential miRNA gene targets were investigated. Results A subset of miRNAs were differentially expressed between allergic and non-allergic asthmatic individuals. Alterations in expression of miR-155, −146a, −374a and − 145 were observed in allergic asthmatics in response to inhaled corticosteroid usage. Additionally, miR-223 and miR-374a expression varied in non-allergic asthmatics based on blood eosinophil numbers. Numerous clinical parameters, including lung function measurements, correlated with subsets of miRNAs. Finally, pathway analysis revealed a potential role for inhaled corticosteroid induced miRNAs in leukocyte regulation, IL-6 signaling and glucocorticoid response. Conclusion Circulating miRNA expression was altered in subjects with allergic and non-allergic asthma and correlated to clinical parameters including lung function and potential gene targets involved in immune processes. This combination of clinical and molecular data may be a basis for the further, more precise classification of asthma subgroups. Taken together, these findings would further asthma research and benefit future patients through the discovery of molecular mechanisms as well as identifying asthma subgroups contributing to the development of personalized medicine.

Background: Allergic rhinitis is characterized by a chronic inflammation of nasal mucosa and represents a risk factor for asthma occurrence. H1 antihistamines reduce the symptoms of rhinitis, but some compounds may have anti-inflammatory properties. Aims: We evaluated the plasma level of some cytokines in patients with persistent allergic rhinitis (PAR) and their evolution after a 4-week treatment with H1 antihistamines, as well as the risk of asthma after 1.5 years. Study Design: Randomized clinical trial. Methods: Eighty-five patients with PAR and 30 healthy volunteers were included in the study. The patients with PAR were randomly divided into 2 groups: 41 patients treated with 5 mg/day desloratadine and 44 patients under 5 mg/day levocetirizine for 4 weeks. The clinical and biological evaluations were performed before and after treatment and included rhinitis symptoms and total symptoms score, type of sensitization, and plasmatic levels of total IgE, IL-1β, IL-6, IL-8 and TNF-α. Results: IL-8 and TNF-α were significantly increased in patients with PAR compared to healthy volunteers (5.85 vs 3.12, p<0.001 and 2.32 vs 1.06, p<0.001, respectively). Both H1 antihistamines reduce all symptoms of allergic rhinitis, including nasal congestion and the plasmatic level of IL-1β, IL-6, IL-8 and TNF-α, after 4 weeks of treatment. The reduction of cytokine levels was not influenced by patients' age, sex, duration or severity of rhinitis, or type of sensitization. Levocetirizine has a superior effect compared to desloratadine in reducing the rhinitis symptoms and cytokines' level. Twenty eight (32.9%) of the patients presented asthma symptoms after 1.5 years. The occurrence of asthma was influenced by house dust sensitization (OR-14.6; CI 95% 1.8-116.3; p=0.01), but baseline values of cytokines were not predictive factors for its appearance. Conclusion: Levocetirizine and desloratadine as a prolonged therapy reduce plasmatic levels of some proinflammatory cytokines in patients with PAR. Levocetirizine has a better effect on decreasing the symptoms and plasmatic levels of IL-1β and IL-8. (ClinicalTrials. gov Identifier: NCT02507635) Founding: POSDRU and University of Medicine and Pharmacy, Iuliu Haţieganu, Cluj Napoca.

Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from severe COVID-19 patients every third to seventh day during hospitalization and every third month after recovery. We profiled their antigen-specific immune cell dynamics by combining single cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE)-Seq, B cell receptor (BCR)-Seq with oligotagged antigen baits. While the proportion of Spike Receptor Binding Domain-specific memory B cells (MBC) increased from 3 months after infection, the other Spike-and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen specific cells, which was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to one year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen specific B cell responses in longitudinally sampled COVID-19 infected patients.

Background and Objectives: The evolution of allergic rhinitis to asthma is a part of “atopic march”. The aim of this study was to analyze possible predictive markers for asthma occurrence in patients with allergic rhinitis to house dust mites (HDM). Materials and Methods: Fifty-eight patients with persistent allergic rhinitis (PAR) were included. The clinical, biological evaluation and fractionated exhaled nitric oxide (FeNO) measurement were performed at enrolment. The patients were clinically evaluated after one year to determine asthma occurrence. Results: The severity of rhinitis symptoms, levels of total immunoglobulin E (IgE), ICAM-1, VCAM-1, E-selectin and IL-6, but not IL-8 and TNF-α were higher in patients with allergic rhinitis who developed asthma compared to non-asthmatics, but the differences were not significant to considered them as predictive factors for asthma occurrence. The risk of asthma was independently influenced by patients aged over 30 years ((OR-3.74; CI95% 0.86–16.31; p = 0.07), a duration of allergic rhinitis over 12 months ((OR-4.20; CI95% 0.88–20; p = 0.07) and a basal FeNO over 28 parts per billion (pbb) ((OR-18.68; CI95% 3.79–92.05; p < 0.001). Conclusion: Clinical and biological parameters may predict asthma occurrence in patients with persistent allergic rhinitis to HDM. Adult patients with a longer duration of rhinitis symptoms and a high level of FeNO have a greater risk to develop asthma.