TY - JOUR AB - Background: Chronic rhinosinusitis is a common disease with a significant impact on the quality of life. Topical drug delivery to the paranasal sinuses is not efficient to prevent sinus surgery or expensive biologic treatment in a lot of cases as the affected mucosa is not reached. More efficient approaches for topical drug delivery are, therefore, necessary. In the current study, dual-energy CT (DECT) imaging was used to examine sinus ventilation before and after sinus surgery using a pulsating xenon gas ventilator in a cadaver head. Methods: Xenon gas was administered to the nasal cavity of a cadaver head with a laminar flow of 7 L/min and with pulsating xenon-flow (45 Hz frequency, 25 mbar amplitude). Nasal cavity and paranasal sinuses were imaged by DECT. This procedure was repeated after functional endoscopic sinus surgery (FESS). Based on the enhancement levels in the different sinuses, regional xenon concentrations were calculated. Results: Xenon-related enhancement could not be detected in most of the sinuses during laminar gas flow. By superimposing laminar flow with pulsation, DECT imaging revealed a xenon wash-in and wash-out in the sinuses. After FESS, xenon enhancement was immediately seen in all sinuses and reached higher concentrations than before surgery. Conclusion: Xenon-enhanced DECT can be used to visualize and quantify sinus ventilation. Pulsating air-/gas flow was superior to laminar flow for the administration of xenon to the paranasal sinuses. FESS leads to successful ventilation of all paranasal sinuses. AU - Becker, S.* AU - Huppertz, T.* AU - Möller, W.* AU - Havel, M.* AU - Schuster, M.* AU - Becker, A.M.* AU - Sailer, M.* AU - Schuschnig, U.* AU - Johnson, T.R.* C1 - 64809 C2 - 52503 TI - Xenon-enhanced dynamic dual-energy CT is able to quantify sinus ventilation using laminar and pulsating air-/gas flow before and after surgery: A pilot study in a cadaver model. JO - Front. Allergy VL - 3 PY - 2022 SN - 2673-6101 ER - TY - JOUR AB - MicroRNAs (miRs) have gained scientific attention due to their importance in the pathophysiology of allergic diseases as well as their potential as biomarkers in allergen-specific treatment options. Their function as post-transcriptional regulators, controlling various cellular processes, is of high importance since any single miR can target multiple mRNAs, often within the same signalling pathway. MiRs can alter dysregulated expression of certain cellular responses and contribute to or cause, but in some cases prevent or repress, the development of various diseases. In this review article, we describe current research on the role of specific miRs in regulating immune responses in epithelial cells and specialized immune cells in response to various stimuli, in allergic diseases, and regulation in the therapeutic approach of allergen-specific immunotherapy (AIT). Despite the fact that AIT has been used successfully as a causative treatment option since more than a century, very little is known about the mechanisms of regulation and its connections with microRNAs. In order to fill this gap, this review aims to provide an overview of the current knowledge. AU - Jakwerth, C.A. AU - Kitzberger, H. AU - Pogorelov, D. AU - Müller, A. AU - Blank, S. AU - Schmidt-Weber, C.B. AU - Zissler, U.M. C1 - 66377 C2 - 53158 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Role of microRNAs in type 2 diseases and allergen-specific immunotherapy. JO - Front. Allergy VL - 3 PB - Frontiers Media Sa PY - 2022 SN - 2673-6101 ER - TY - JOUR AU - Ferreira, F.* AU - Mueller, G.A.* AU - Gilles, S. AU - Wills-Karp, M.* C1 - 64808 C2 - 52502 TI - Editorial: Activation of innate immunity by allergens and allergenic sources. JO - Front. Allergy VL - 2 PY - 2021 SN - 2673-6101 ER - TY - JOUR AB - Seasonal exposure to birch pollen (BP) is a major cause of pollinosis. The specific role of Toll-like receptor 4 (TLR4) in BP-induced allergic inflammation and the identification of key factors in birch pollen extracts (BPE) initiating this process remain to be explored. This study aimed to examine (i) the importance of TLR4 for dendritic cell (DC) activation by BPE, (ii) the extent of the contribution of BPE-derived lipopolysaccharide (LPS) and other potential TLR4 adjuvant(s) in BPE, and (iii) the relevance of the TLR4-dependent activation of BPE-stimulated DCs in the initiation of an adaptive immune response. In vitro, activation of murine bone marrow-derived DCs (BMDCs) and human monocyte-derived DCs by BPE or the equivalent LPS (nLPS) was analyzed by flow cytometry. Polymyxin B (PMB), a TLR4 antagonist and TLR4-deficient BMDCs were used to investigate the TLR4 signaling in DC activation. The immunostimulatory activity of BPE was compared to protein-/lipid-depleted BPE-fractions. In co-cultures of BPE-pulsed BMDCs and Bet v 1-specific hybridoma T cells, the influence of the TLR4-dependent DC activation on T cell activation was analyzed. In vivo immunization of IL-4 reporter mice was conducted to study BPE-induced Th2 polarization upon PMB pre-treatment. Murine and human DC activation induced by either BPE or nLPS was inhibited by the TLR4 antagonist or by PMB, and abrogated in TLR4-deficient BMDCs compared to wild-type BMDCs. The lipid-free but not the protein-free fraction showed a reduced capacity to activate the TLR4 signaling and murine DCs. In human DCs, nLPS only partially reproduced the BPE-induced activation intensity. BPE-primed BMDCs efficiently stimulated T cell activation, which was repressed by the TLR4 antagonist or PMB, and the addition of nLPS to Bet v 1 did not reproduce the effect of BPE. In vivo, immunization with BPE induced a significant Th2 polarization, whereas administration of BPE pre-incubated with PMB showed a decreased tendency. These findings suggest that TLR4 is a major pathway by which BPE triggers DC activation that is involved in the initiation of adaptive immune responses. Further characterization of these BP-derived TLR4 adjuvants could provide new candidates for therapeutic strategies targeting specific mechanisms in BP-induced allergic inflammation. AU - Pointner, L.* AU - Kraiem, A.* AU - Thaler, M.* AU - Richter, F.* AU - Wenger, M.* AU - Bethanis, A.* AU - Klotz, M.* AU - Traidl-Hoffmann, C. AU - Gilles, S. AU - Aglas, L.* C1 - 64389 C2 - 51839 TI - Birch pollen induces toll-Like receptor 4-dependent dendritic cell activation favoring T cell responses. JO - Front. Allergy VL - 2 PY - 2021 SN - 2673-6101 ER -