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Journal articleGuerrero-Fonseca IM, Hern谩ndez-Almaraz KB, Le贸n-Vega II, et al., 2026, , J Cell Biol, Vol: 225
The adhesive interactions of neutrophils with postcapillary venules during inflammation have been well studied. However, how neutrophils trigger molecular changes in endothelial cells (EC) during their extravasation requires further exploration. The endothelial actin-binding protein cortactin regulates endothelial contacts and neutrophil-endothelial interactions, but the associated mechanisms remain elusive. Hypothesizing that endothelial cortactin dynamics change during inflammation, using super-resolution confocal microscopy of inflamed mouse cremasteric venules and HUVEC, we report that neutrophil interaction with EC induces reduction in EC cortactin levels. This response was specifically mediated by neutrophil serine proteases, including cathepsin G, that were detected inside EC. The observed cortactin degradation was abolished after inhibition of serine proteases or blockade of neutrophil exocytosis. Finally, the endogenous serine protease inhibitor α1-antitrypsin suppressed cortactin degradation in vivo and reduced neutrophil adhesion and extravasation. Collectively, our data unveil a new mechanism by which neutrophils manipulate proteins inside EC to facilitate their extravasation.
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Journal articleYang W, Giblin SP, Pease JE, 2026, , Basic Clin Pharmacol Toxicol, Vol: 139
CXCL17 was recently reported to activate GPR25, a receptor expressed by T-regulatory cells. Although classified as a chemokine, the activity of CXCL17 is ablated by minor C-terminal truncation, suggesting a novel mode of receptor activation. We set out to test this hypothesis by mutagenesis. GPR25 was expressed in the murine pre-B cell line L1.2 and mediated robust migration of transfectants to nanomolar concentrations of recombinant CXCL17 (24-119). The N-terminally truncated form of CXCL17 (64-119) was also chemotactic for GPR25 transfectants, albeit with severely reduced potency. Modelling of CXCL17:GPR25 implied multiple interactions between the N- and C-termini of CXCL17 with GPR25, which was validated by mutagenesis. Cells expressing a chimeric FPR1:GPR25 construct responded chemotactically to CXCL17 but with significantly reduced potency compared with wild-type GPR25 transfectants, implicating the GPR25 N-terminus in CXCL17 recognition. Mutagensis of the GPR25 residues W95, R178 and R264 resulted in a complete loss of chemotactic responsiveness to CXCL17, consistent with the residues interacting with the C-terminal CXCL17 motif. In conclusion, we verify GPR25 as a bona fide CXCL17 receptor and suggest a two-step model of GPR25 activation, in which the receptor N-terminus orients CXCL17 for activation of GPR25 via its C-terminus. We also advocate the reclassification of CXCL17 as a chemoattractant distinct from the chemokine family.
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Journal articleSakamachi Y, Wiley E, Trempus CS, et al., 2026, , Sci Transl Med, Vol: 18
Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation that results from maladaptive responses to lung epithelial injury; however, the underlying mechanisms remain unclear, and treatment options are limited. Here, we showed that deficiency in the innate immune receptor toll-like receptor 5 (TLR5) is associated with IPF in humans and with increased susceptibility to bleomycin-induced pulmonary fibrosis in mice and that activation of lung epithelial TLR5 through a synthetic flagellin analog protected mice from experimental fibrosis. Mechanistically, epithelial TLR5 activation induced antimicrobial gene expression and ameliorated lung dysbiosis after injury. In contrast, TLR5 deficiency in mice and patients with IPF was associated with lung dysbiosis. Elimination of the microbiome in mice through administration of antibiotics abolished the protective effect of TLR5, and reconstitution of the microbiome by fecal microbiota transplantation rescued the observed phenotype. In conclusion, these studies revealed that TLR5 protects against pulmonary fibrosis through effects on the lung microbiota, providing insight into therapeutic approaches that may ultimately benefit patients with IPF.
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Journal articleChin D, Hernandez-Beeftink T, Donoghue L, et al., 2026, , Eur Respir J
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Journal articleKonstantinidi R, Yates L, Lloyd C, et al., 2026,
Investigating the impact of PBAE-mediated FOXJ1 mRNA delivery on differentiation of primary human bronchial epithelial cells
, Biology Open, ISSN: 2046-6390Primary human basal bronchial epithelial cells (HBECs) are an important population of progenitor cells capable of self-renewal and differentiation to maintain airway homeostasis. At air-liquid interface (ALI) culture, HBECs undergo mucociliary differentiation, providing a robust physiologic model to evaluate novel therapeutics such as in vitro transcribed messenger RNA (IVT-mRNA). However, the impact of IVT-mRNA delivery on the differentiation potential of basal HBECs remains poorly characterised. Poly (beta amino) ester (PBAE) nanoparticles have demonstrated effective airway delivery of IVT-mRNA in various pre-clinical studies. Here, we aimed to understand the impact of PBAE-mediated mRNA transfection on basal HBEC differentiation at ALI. We investigated IVT-mRNA encoding the ciliogenesis transcription factor Forkhead box J1 (FOXJ1) as a model tool for transient overexpression in primary basal HBECs and characterised its subsequent impact on epithelial integrity and differentiation at ALI. PBAE-mediated delivery of FOXJ1 mRNA to submerged primary HBECs resulted in approximately 50% FOXJ1-positive cells and transient upregulation of key ciliogenesis-related genes, including DNALI1 and RSPH9. Following 28 days of differentiation at ALI, FOXJ1 or reporter mRNA transfected cultures displayed normal epithelial morphology, with tight junction and differentiation markers, proportions of secretory and ciliated cells, and cilia ultrastructure comparable to non-transfected controls. These data indicate that PBAE-mediated IVT-mRNA delivery can transiently increase encoded protein expression in basal primary HBECs, without impeding mucociliary differentiation.
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Journal articlede Benedictis FM, Beasley R, Pavord I, et al., 2026, , Lancet Respir Med
Inhaled corticosteroids are the foundation of asthma therapy and now, 50 years on from their introduction, is an appropriate time to summarise some of the key studies that have progressed the field. We can now make better decisions in selecting the optimal inhaled corticosteroid-based regimens and identifying likely responders, based on biomarkers and patient characteristics. Inhaled corticosteroids reduce the risk of asthma attacks, but do not alter the course of the disease. Asthma remission, which is as yet an undefined therapeutic goal, is the aim, but the role of inhaled corticosteroids is unclear. High-dose inhaled corticosteroid therapy can cause systemic adverse events, suggesting that steps be taken to avoid this through the addition of long-acting β2-adrenergic agonists and the judicious use of biologics. Researchers will continue to learn more about the advantages and limitations of inhaled corticosteroids as they explore methods of disease prevention and remission in the future with new tools and treatments.
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Journal articleOgbogu PU, Roufosse F, Akuthota P, et al., 2026, , Nat Med
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Journal articleSousa-Pinto B, Vieira RJ, Gil-Mata S, et al., 2026, , Allergy
BACKGROUND: To achieve adequate symptom control, patients with allergic rhinitis (AR) often need to increase their medication dose or add other treatments (co-medication). We aimed to perform a systematic review to compare the efficacy and safety of AR medications for increased dose versus co-medication. METHODS: We searched four bibliographic databases and three trial databases for randomised controlled trials assessing the effect of intranasal and/or oral medications in patients of all ages with seasonal or perennial AR. We performed pairwise meta-analysis based on direct evidence to compare (i) non-standard versus standard treatment doses, and (ii) co-medication strategies versus monotherapy using standard doses. Furthermore, we fitted dose-response network meta-analysis (NMA) to obtain projected estimates for comparisons involving two times the standard dose of AR medications in monotherapy versus co-medication with the standard dose of the same medications. We assessed the certainty of evidence using GRADE for NMA. RESULTS: We included 262 studies. Co-medication schemes involving oral antihistamines (OAH) + intranasal corticosteroids (INCS) resulted in higher improvements of nasal symptoms and quality of life than doubling the dose of OAH. However, doubling the dose of intranasal medications led to better results than having intranasal medications + OAH. Doubling the dose of INCS was associated with higher efficacy than adding intranasal antihistamines (INAH). No relevant safety differences were found between treatment strategies. CONCLUSIONS: Results favoured (i) doubling the dose of intranasal medications versus adding OAH, and (ii) adding INCS to OAH over doubling the dose of OAH. This study will inform the ARIA-EAACI 2024-2025 guidelines.
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Journal articleJenkins RG, 2026, , Nat Immunol, Vol: 27, Pages: 890-891
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Journal articleZheng Y, Li Y, Zeyneloglu C, et al., 2026, , Allergy, Vol: 81, Pages: 1397-1432
The post-COVID pandemic era has witnessed a concerning resurgence of respiratory viruses, driving a global increase in acute respiratory infections. This trend may stem from relaxed non-pharmaceutical interventions, waning herd immunity, immunological imprinting limiting heterosubtypic protection, or viral antigenic evolution. This review aims to identify and characterize risk and protective factors associated with infection, hospitalization, severe illness, and mortality, while elucidating the drivers of the rising incidence of respiratory virus infections post-pandemic. Evidence on SARS-CoV-2 sublineages, influenza, respiratory syncytial virus, rhinovirus, adenovirus, human metapneumovirus, human parainfluenza virus, human coronaviruses, and cytomegalovirus has been collected and identified. Identified risk factors include demographic characteristics such as pediatrics and older age, male sex, race (Black, Hispanic, American Indian or Alaska native), preterm birth, and HLA-DQA1, IFNAR2, ST6GAL, and B3GALT5 genetic susceptibility. Behavioral, socioeconomic (low socioeconomic status, crowded living conditions), environmental influences (cold seasons, pollution), smoking, obesity and malnutrition could also exacerbate the risk of infection and adverse outcomes. Comorbidities, such as chronic conditions and immunocompromised states, significantly increase the risk of severe disease and hospitalization. Laboratory indices linked to severe disease outcomes include neutrophilia or neutropenia, lymphopenia, eosinopenia, and elevated C-reactive protein. Viral subtypes, viral load kinetics, vaccination status, and antiviral therapies further delineate risk profiles. Epithelial barrier impairment and underlying chronic airway diseases characterized by type 2 immunity also play a detrimental role in the development and severity of respiratory viral infections. Our findings highlight the need for stratified prevention strategies, which combine universal measures targeting shar
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Journal articleMarques-Mejias A, Bartha I, Ciaccio CE, et al., 2026, , Ann Allergy Asthma Immunol, Vol: 136
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Journal articleWallace DV, Hossny EM, Levin M, et al., 2026, , Immunol Allergy Clin North Am, Vol: 46, Pages: 233-256
This article compares 12 national and international anaphylaxis guidelines published between 2006 and 2025, highlighting evolving methodological frameworks, diagnostic criteria, and treatment approaches. While consensus supports prompt epinephrine use, differences remain in definitions, risk stratification, and post-acute care. Gaps in education, early childhood care protocols, and global harmonization continue to exist. The analysis emphasizes the shift from crisis-based to proactive anaphylaxis management and underscores the need for equity-focused, evidence-based interventions.
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Journal articleSory DR, Heyraud ACM, Jones JR, et al., 2026, , Adv Healthc Mater, Vol: 15
This article addresses the unmet clinical need of scaffolds for bone regeneration that can combine osteogenic properties, such as the promotion of bone marrow stem cell differentiation into osteoblasts, with the ability to withstand cyclic loading. In our previous study, we demonstrated that discs of SiO2-CaOCME/poly(tetrahydrofuran)/poly(caprolactone) hybrids or their dissolution products can drive terminal osteogenic differentiation of human bone marrow stromal cells (h-BMSCs) in vitro. The current study shows that the 3D-printed hybrid scaffolds with physiologically relevant 3D architecture further promote h-BMSC osteogenesis. The 3D-printed scaffolds support spatially organized cell behavior in an environment mirroring conditions relevant to off-the-shelf implant applications. Primary cellular functions, including viability, adhesion, and proliferation, were maintained across 3D scaffold surfaces and within inter-strut regions. osteogenic commitment was evidenced by the upregulation of lineage-specific transcripts, hydroxyapatite deposition, and the organized assembly of extracellular matrix (ECM) proteins. Our results demonstrate that 3D-printed scaffolds drive osteogenesis by modulating cell metabolism, inducing osteogenic morphological transitions, and promoting the expression of osteocalcin and collagen type I alpha 1 chain, alongside hydroxyapatite matrix mineralization. Collectively, our findings highlight the SiO2-CaOCME/poly(tetrahydrofuran)/poly(caprolactone) scaffold's strong osteogenic properties-driven by composition, surface architecture, and ion release - and its promise for clinical bone regeneration.
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Journal articleYin X, Meng J, Durham SR, et al., 2026, , Allergy, Vol: 81, Pages: 1327-1330
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Journal articleBush A, 2026, , Allergol Int
The areas covered represent a personal selection in the field. Asthma is defined in this manuscript as a clinical syndrome of wheeze, breathlessness and chest tightness, sometimes with excess cough. No assumptions are made about underlying pathology, and asthma thus becomes a clinical description, not a diagnosis. The areas covered include the need never to forget the importance of getting the basics right, including correct diagnosis and appropriate management; most children with asthma do not need biologics. Recent advances in preschool wheeze are covered next, especially the beginnings of phenotype-driven treatment, and the difficult issue of understanding non-eosinophilic wheezing. It is becoming clearer that infection likely plays a big role, but management is very difficult with no evidence base. We are now coming to realize the importance of phenotyping acute asthma attacks; one size does not fit all, but whereas many are eosinophilic, some are infection driven and are non-eosinophilic, especially in the preschool years. A phenotypic approach may allow us to reduce the burden of repeated oral corticosteroid bursts. Furthermore, we need to move beyond mere cell counting to assessing functional status. We are increasingly appreciating the importance of replacing short-acting β-2 agonist reliever therapy with combined inhaled corticosteroid and a fast acting short- and especially long-acting β-2 agonists. Finally, the use of biologicals in severe asthma is discussed. The possibility that early use of biologics may induce remission or even cure asthma.
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Journal articleKlimek L, Mullol J, Reitsma S, et al., 2026, , Allergy
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Journal articleSafavi S, Smith S, Jahnke N, et al., 2026, , Cochrane Database Syst Rev, Vol: 4
RATIONALE: Cystic fibrosis (CF) is an inherited multi-organ disorder. People with CF (pwCF) experience recurrent and chronic lung infections and a progressive loss of lung function. PwCF with poor and rapidly declining lung function may be considered for lung transplantation (LTx), which may improve their quality of life and survival. Nontuberculous mycobacteria (NTM) can cause pulmonary disease in pwCF, and NTM infection is a poor prognostic factor in LTx. Guidelines recommend NTM infection should not automatically preclude LTx. It is important to evaluate the evidence base for LTx in pwCF and NTM pulmonary disease. OBJECTIVES: To evaluate clinical outcomes in pwCF and with NTM infection (NTM infection alone or with NTM pulmonary disease) who undergo LTx by comparing: 1. pwCF with current NTM lung infection who undergo LTx versus those with NTM infection who do not undergo LTX; 2. pwCF with current NTM lung infection who undergo LTx versus those without NTM undergoing LTx. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, CENTRAL, MEDLINE, Embase, and PubMed as well as two ongoing trials registries. We checked references. The latest search date was 17 February 2026. ELIGIBILITY CRITERIA: We considered non-randomised studies of pwCF (any age) with or without NTM lung infection or disease being considered for LTx as well as studies of pwCF and NTM who either did or did not undergo LTx. OUTCOMES: Our critical outcomes were mortality, disseminated NTM infection post-LTx, time to chronic lung allograft dysfunction (CLAD), and quality of life at any time points reported. We additionally planned to report lung function, hospitalisations for pulmonary exacerbations, and nutritional parameters in the review. RISK OF BIAS: We assessed the risk of bias in three studies using ROBINS-I and in one study using the Joanna Briggs Institute checklist for case series. SYNTHESIS METHODS: We could only report results narratively. We used GRADE to assess the cert
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Journal articleScheire S, Lourijsen E, Blauwblomme M, et al., 2026, , Allergy
Systemic glucocorticosteroids (sGCS) are widely used in the treatment of chronic inflammatory airway diseases such as rhinitis, rhinosinusitis and asthma. It is well-known that systemic use is linked to multiple adverse effects (AEs) both in the short- and the long-term. However, less is known about the safety of multiple short courses of sGCS. Currently there is no established agreement on the acceptable cumulative exposure to sGCS, considering the potential for various AEs. This systematic review and meta-analysis evaluated sGCS-related AEs in both upper and lower inflammatory airway disease, with a particular focus on short- and long-term risks. We further evaluated whether a dose-response relationship existed between the daily and cumulative dosages of sGCS and the occurrence of those AEs. Our meta-analysis confirmed that cumulative dosages between 500 mg and 1 g prednisolone-equivalent significantly increase the risk of most AEs, with risks increasing with incremental dose. These findings underscore the importance of: (a) judicious sGCS prescription and need for steroid stewardship, due to their potential for short- and long-term complications, occurring even with repeated short courses, and (b) prioritization of steroid-sparing approaches (e.g., biologicals) to avoid reaching a cumulative dose of 500 mg.
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Journal articleMakuyana N, Seldeslachts L, Michiels L, et al., 2026, , Sci Immunol, Vol: 11
Respiratory infections that result in severe and life-threatening immune-mediated respiratory decline are a major public health issue. Controlling local respiratory immune reactions without the use of systemic immunosuppressants remains an unmet clinical challenge. We developed a gene delivery system to express anti-inflammatory cytokines in the lung, which reestablishes local immune homeostasis without triggering systemic effects. Using an adeno-associated vector cargo system (AAV6.2-CC10), we induced production of interleukin-2 (IL-2), IL-1 receptor antagonist (IL-1RA), and IL-10 in situ in the lung microenvironment, with no detectable expression or immunological deviation in the peripheral immune system. We demonstrate the effective potential of IL-2, IL-1RA, and IL-10 as immunomodulatory cargos in severe infectious challenge, which reduced respiratory pathology after influenza-associated pulmonary aspergillosis. Thus, the AAV6.2-CC10 platform enables targeted delivery of biologics to the lung, modulates the lung environment, and improves pathology without inducing systemic immune reactions.
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Journal articleMohammed Abdul Wajid L, Saglani S, Nagakumar P, et al., 2026, , Arch Dis Child, Vol: 111, Pages: 444-448
OBJECTIVE: This study aimed to explore health professionals' perspectives on the management of preschool wheeze, including their views on using tests to guide treatment for children with recurrent wheeze. DESIGN: Purposive and snowball sampling were used in this qualitative study to recruit health professionals with experience of managing children with pre-school wheeze from primary and secondary care settings across England. Semi-structured interviews were conducted via Microsoft Teams. Transcripts were analysed thematically, supported by the use of NVivo software, to identify key themes. RESULTS: 14 health professionals participated: four general practitioners, four general paediatricians, four hospital asthma nurses, one tertiary respiratory paediatrician and one primary care nurse. Participants agreed that preschool wheeze remains a significant disease. Thematic analysis identified four key themes: (1) challenges with diagnostic terminology, where a lack of consistent terminology was considered to impact communication and management; (2) diagnostic uncertainty, where the absence of objective tests for early asthma diagnosis negatively contributed to management plans; (3) current practice of investigating children with preschool wheeze, where participants described a lack of infrastructure and approach to performing tests in primary and secondary care; and (4) treatment considerations in which parents' medication beliefs were thought to influence adherence to prescribed treatments. There were differences in the views regarding the management of preschool wheeze between primary and secondary care professionals. CONCLUSION: Health professionals' views highlight inconsistent use of diagnostic terminology for preschool wheeze, contributing to variation in management. Integrated care pathways and infrastructure are urgently needed to improve outcomes for children with preschool wheeze.
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