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Dendritic cells (DCs) control the balance between protection against pathogens and tolerance to innocuous or self-antigens. Here, we demonstrate for the first time that mouse plasmacytoid DCs (pDCs) can be segregated into three distinct populations, exhibiting phenotypic and functional differences, according to their surface expression of CD8α or CD8β as CD8α−β−, CD8α+β−, or CD8α+β+. In a mouse model of lung inflammation, adoptive transfer of CD8α+β− or CD8α+β+ pDCs prevents the development of airway hyper-reactivity. The tolerogenic features of these subsets are associated with increased production of retinoic acid, which leads to the enhanced induction of Foxp3+ regulatory T cells compared with CD8α−β− pDCs. Our data thus identify subsets of pDCs with potent tolerogenic functions that may contribute to the maintenance of tolerance in mucosal sites such as the lungs. [ABSTRACT FROM AUTHOR]

Abstract: Sublingual immunotherapy (SLIT) is a non-invasive and efficacious treatment for type I respiratory allergies. To identify candidate adjuvants and galenic formulations capable of inducing tolerance by the sublingual route, an initial screening was carried out using in vitro cocultures of human monocyte-derived dendritic cells and naïve CD4+ T cells. Selected molecules were subsequently tested in a murine asthma model of sublingual immunotherapy in BALB/c mice sensitized to ovalbumin. In this model, we evaluated bronchial hyperreactivity (measured by whole-body plethysmography), pulmonary inflammation (evaluated histologically), and type 2 humoral and cellular immune responses monitored by Elisa and Elispot techniques in mice sensitized with either soluble or with adjuvant-formulated ovalbumin. Four categories of adjuvant known to increase IL-10+/−IFNγ production by naïve CD4+ T cells (Treg/Th1) were found to enhance SLIT efficacy in vivo in these mice. These adjuvants were: vitamin D3/dexamethasone, Lactobacillus plantarum, the TLR2 agonist Pam3CSK4, and the TLR4 synthetic ligand OM-294-BA-MP. In addition, sublingual administration of ovalbumin combined with mucoadhesive maize-derived maltodextrin increased sublingual tolerance induction by targeting oral dendritic cells and ovalbumin-specific T cells in cervical and submaxillary lymph nodes. In conclusion, better understanding of specific immune responses to allergen at the level of the sublingual mucosa may lead to the development of new sublingual vaccines. In the future, such vaccines would incorporate Th1/Treg adjuvants, as well as mucoadhesive galenic formulations that target dendritic cells in the sublingual mucosa. [Copyright &y& Elsevier]

Introduction L’immunothérapie allergénique (ITA) est aujourd’hui prescrite aux patients en fonction de la réactivité de leurs IgE à des allergènes spécifiques, mesurée par test cutané ou dosage in vitro. L’identification de biomarqueurs prédisant l’efficacité de l’ITA permettrait d’améliorer nettement la sélection des patients répondant à ce traitement. Méthodes Les échantillons de sérum prélevés avant traitement chez 82 patients allergiques aux pollens de graminées recevant une ITA par voie sublinguale ont été analysés par électrophorèse bidimensionnelle quantitative (2D-DiGE) et spectrométrie de masse sans marquage. Le rôle de la Fétuine-A dans l’allergie a été adressé par extinction du gène correspondant à cette protéine dans un modèle murin d’asthme à l’ovalbumine ainsi que l’utilisation de tests de stimulation in vitro de cellules dendritiques humaines et de la résonance plasmonique de surface. Résultats Par des approches de protéomique quantitative, nous avons montré que les taux de Fétuine-A sialylée étaient plus élevés avant traitement dans le sérum des patients répondant à l’ITA, en comparaison avec les patients non-répondeurs. La Fétuine-A est impliquée dans de nombreux processus inflammatoires mais son rôle dans l’allergie n’a pas été étudié jusqu’à présent. L’extinction du gène de la Fétuine-A dans un modèle murin d’asthme allergique augmente fortement l’hyperréactivité bronchique et les réponses Th2 après sensibilisation à l’ovalbumine. La Fétuine-A, sialylée ou non, se fixe au LPS, mais seule la forme sialylée agit en synergie avec le LPS, les allergènes de pollens de graminées ou d’acariens pour augmenter les propriétés pro-allergiques des cellules dendritiques humaines par une voie dépendante de TLR4. Conclusion La quantification de la Fétuine-A sialylée sérique permet d’identifier, avant traitement, les patients ayant une plus forte probabilité de bénéficier de l’ITA aux pollens de graminées. Des études impliquant de grandes cohortes de patients allergiques aux pollens de graminées ou aux acariens sont en cours pour valider la pertinence de ce candidat biomarqueur prédictif de l’efficacité de l’ITA avant traitement. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "CD8 subunit expression by plasmacytoid dendritic cells is variable, and does not define stable subsets," by A. S. Brown, D. Bourges, D. K. Ang, E. L. Hartland and I. R. van Driel in the 2014 issue.

To analyze early and late clinical outcomes of malnourished patients undergoing heart transplantation. We retrospectively evaluated all patients ≥18 years of age, who received a heart transplant between January 2015 and July 2020 at our center. For each patient, we calculated the semi-quantitative Malnutrition Universal Screening Tool (MUST) score at the time of transplantation to assess the patient nutritional status. A Cox regression analysis was performed to assess follow-up mortality and postoperative complications risk. Data from 177 patients (median age 58, IQR 49-65; M 134, 76%) were collected. Median preoperative BMI was 24kg/mq (IQR 21-28). Preoperative MUST score was 0, 1, 2 or >2 in 100 (57%), 24 (14%), 40 (23%) and 12 (6%) patients, respectively. Median preoperative eGFR was 64 ml/min (IQR 49-83). An increase in MUST score (from 0 to 2) was not associated with higher in-hospital mortality (hazard ratio 0.99, 95% CI 2.06-0.45, p=0.99), and was only related to increased risk of postoperative acute kidney injury requiring renal replacement therapy (hazard ratio 2.04, 95% CI 1.06-3.95, p=0.033) or septicemia (hazard ratio 3.37, 95% CI 1.08-10.54, p=0.036) within 24 hours after transplantation. Postoperative data and associated hazard ratios are summarized in Table 1. Survival rates at 3 and 5 years were respectively 77% (95% CI 71-84, patients at risk n=83) and 73% (95 CI 66-82, patients at risk 28). An analogous increase in MUST score was associated with increased follow-up mortality risk (hazard ratio 1.67, 95% CI 1.07-2.61, p=0.025). Severe malnutrition (evaluated with a multi-variable semi-quantitative parameter as MUST score) in patients receiving heart transplantation is a risk factor for late death. However, it is not associated with increased in-hospital mortality or major postoperative complications except for early septicemia or renal function. [ABSTRACT FROM AUTHOR]

Patients suffering from Alzheimer’s disease, Parkinson disease with dementia, and diffuse cerebrovascular dementia show different features of cortical sources of resting state electroencephalographic (EEG) rhythms (Babiloni et al., 2004, 2011). Here, we tested the hypothesis that stroke patients are characterized by peculiar abnormalities of these rhythms. Resting state eyes-closed EEG data were recorded in 29 acute stroke, 29 Alzheimer’s disease, 29 mild cognitive impairment patients, and 29 cognitively intact elderly subjects. Stroke patients were age matched with the other groups, they showed a mild cognitive decline. EEG recordings were performed from the 20th to 30th days from the first ischemic or hemorrhagic acute event. LORETA was used for source estimation. Compared to the other groups, the stroke patients were characterized by a greater power of widespread cortical sources of delta (1–4Hz) and theta (4–8Hz) rhythms (p <0.05). Abnormal cortical sources of delta and theta rhythms reflect the effects of stroke on cortical neural synchronization. The present study motivates future research evaluating the clinical value of delta sources for the prediction of the patients’ recovery and possible cognitive symptoms. [Copyright &y& Elsevier]