Ablation of CCL17-positive hippocampal neurons induces inflammation-dependent epilepsy.

Objective: Neuronal cell death and neuroinflammation are characteristic features of epilepsy, but it remains unclear whether neuronal cell death as such is causative for the development of epileptic seizures. To test this hypothesis, we established a novel mouse line permitting inducible ablation of pyramidal neurons by inserting simian diphtheria toxin (DT) receptor (DTR) cDNA into the Ccl17 locus. The chemokine CCL17 is expressed in pyramidal CA1 neurons in adult mice controlling microglial quiescence.

Topographical variations in the skin barrier and their role in disease pathogenesis.

The skin barrier can be divided into at least four functional units: chemical, microbial, physical and immunological barriers. The chemical and microbial barriers have previously been shown to exhibit different characteristics in topographically distinct skin regions. There is increasing evidence that the physical and immunological barriers also show marked variability in different areas of the skin.

IL-9 sensitizes human T2 cells to proinflammatory IL-18 signals in atopic dermatitis.

Background: T2 cells crucially contribute to the pathogenesis of atopic dermatitis (AD) by secreting high levels of IL-13 and IL-22. Yet the upstream regulators that activate T2 cells in AD skin remain unclear. IL-18 is a putative upstream regulator of T2 cells because it is implicated in AD pathogenesis and has the capacity to activate T cells.

Dominant immune tolerance in the intestinal tract imposed by RelB-dependent migratory dendritic cells regulates protective type 2 immunity.

Dendritic cells (DCs) are crucial for initiating protective immune responses and have also been implicated in the generation and regulation of Foxp3 regulatory T cells (Treg cells). Here, we show that in the lamina propria of the small intestine, the alternative NF-κB family member RelB is necessary for the differentiation of cryptopatch and isolated lymphoid follicle-associated DCs (CIA-DCs). Moreover, single-cell RNA sequencing reveals a RelB-dependent signature in migratory DCs in mesenteric lymph nodes favoring DC-Treg cell interaction including elevated expression and release of the chemokine CCL22 from RelB-deficient conventional DCs (cDCs).

European pollen reanalysis, 1980-2022, for alder, birch, and olive.

The dataset presents a 43 year-long reanalysis of pollen seasons for three major allergenic genera of trees in Europe: alder (Alnus), birch (Betula), and olive (Olea). Driven by the meteorological reanalysis ERA5, the atmospheric composition model SILAM predicted the flowering period and calculated the Europe-wide dispersion pattern of pollen for the years 1980-2022. The model applied an extended 4-dimensional variational data assimilation of in-situ observations of aerobiological networks in 34 European countries to reproduce the inter-annual variability and trends of pollen production and distribution.

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial.

Importance: Psoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies.

Objective: To evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis.

Design, Setting, And Participants: The GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis.

CCR3-dependent eosinophil recruitment is regulated by sialyltransferase ST3Gal-IV.

Eosinophil recruitment is a pathological hallmark of many allergic and helminthic diseases. Here, we investigated chemokine receptor CCR3-induced eosinophil recruitment in sialyltransferase mice. We found a marked decrease in eosinophil extravasation into CCL11-stimulated cremaster muscles and into the inflamed peritoneal cavity of mice.

The atypical IκB family member Bcl3 determines differentiation and fate of intestinal RORγt regulatory T-cell subsets.

Peripherally-induced regulatory T cells (pTregs) expressing the retinoic acid receptor-related orphan-receptor gamma t (RORγt) are indispensable for intestinal immune homeostasis. Nuclear factor kappa family members regulate the differentiation of thymic Tregs and promote their survival in the periphery. However, the Treg intrinsic molecular mechanisms controlling the size of the pTregs in the intestine and associated lymphoid organs remain unclear.

TGF-β specifies T versus T17 cell fates in murine CD4 T cells through c-Maf.

T follicular helper (T) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse T cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-β (TGF-β) induces robust expression of T hallmark molecules CXCR5 and Bcl6 in activated mouse CD4 T cells in vitro. TGF-β-induced mouse CXCR5 T cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated T cells and provide critical help to B cells.

17q21 Variants Disturb Mucosal Host Defense in Childhood Asthma.

The strongest genetic risk factor for childhood-onset asthma, the 17q21 locus, is associated with increased viral susceptibility and disease-promoting processes. To identify biological targets underlying the escalated viral susceptibility associated with the clinical phenotype mediated by the 17q21 locus. Genome-wide transcriptome analysis of nasal brush samples from 261 children (78 healthy, 79 with wheezing at preschool age, 104 asthmatic) within the ALLIANCE (All-Age-Asthma) cohort, with a median age of 10.

In Vitro Study of TLR4-NLRP3-Inflammasome Activation in Innate Immune Response.

Toll-like receptors (TLRs) are pivotal players in mediating immune responses. TLR4 is the main receptor for LPS, a strong activator of immune cells. LPS/TLR4-dependent pathway, by inducing NF-κB activation, is responsible for the release of several mediators, including IL-1β, one of the most powerful cytokines deeply involved in inflammatory and immune responses.

Impact of asthma in Europe: A comparison of web search data in 21 European countries.

Background: Asthma is a chronic inflammatory disorder of the airways and one of the most important non-communicable diseases worldwide. Analyzing crowdsourced data can help understand public interest and unmet needs as well as potential factors influencing search behavior.

Objective: The study aimed to investigate asthma-related web search data in Europe to identify possible regional and seasonal variations and to assess public interest.

Towards European automatic bioaerosol monitoring: Comparison of 9 automatic pollen observational instruments with classic Hirst-type traps.

To benefit allergy patients and the medical practitioners, pollen information should be available in both a reliable and timely manner; the latter is only recently possible due to automatic monitoring. To evaluate the performance of all currently available automatic instruments, an international intercomparison campaign was jointly organised by the EUMETNET AutoPollen Programme and the ADOPT COST Action in Munich, Germany (March-July 2021). The automatic systems (hardware plus identification algorithms) were compared with manual Hirst-type traps.

Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases.

Abundant heterogeneous immune cells infiltrate lesions in chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-promoting from bystander immune cells. Here, we investigate the landscape of non-communicable inflammatory skin diseases (ncISD) by spatial transcriptomics resulting in a large repository of 62,000 spatially defined human cutaneous transcriptomes from 31 patients. Despite the expected immune cell infiltration, we observe rather low numbers of pathogenic disease promoting cytokine transcripts (IFNG, IL13 and IL17A), i.

The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis.

In recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients.

Drivers of the release of the allergens Bet v 1 and Phl p 5 from birch and grass pollen.

The drivers affecting the Pollen Allergen Potency (PAP, amount of allergen released per pollen) are sparsely known. Betula and Poaceae airborne pollen are the two main allergenic pollen in the World. Airborne pollen and their allergens Bet v 1 and Phl p 5 were simultaneously measured from 2010 to 2015 in Davos (Switzerland) and Munich (Germany) by using volumetric traps and ChemVol cascade impactors.

Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation.

The lung epithelial barrier serves as a guardian towards environmental insults and responds to allergen encounter with a cascade of immune reactions that can possibly lead to inflammation. Whether the environmental sensor aryl hydrocarbon receptor (AhR) together with its downstream targets cytochrome P450 (CYP1) family members contribute to the regulation of allergic airway inflammation remains unexplored. By employing knockout mice for AhR and for single CYP1 family members, we found that AhR and CYP1B1 but not CYP1A1 or CYP1A2 animals display enhanced allergic airway inflammation compared to WT.

NF-κB in control of regulatory T cell development, identity, and function.

Regulatory T cells (Treg cells) act as a major rheostat regulating the strength of immune responses, enabling tolerance of harmless foreign antigens, and preventing the development of pathogenic immune responses in various disease settings such as cancer and autoimmunity. Treg cells are present in all lymphoid and non-lymphoid tissues, and the latter often fulfill important tasks required for the physiology of their host organ. The activation of NF-κB transcription factors is a central pathway for the reprogramming of gene expression in response to inflammatory but also homeostatic cues.

Requirements and expectations of high-quality biomarkers for atopic dermatitis and psoriasis in 2021-a two-round Delphi survey among international experts.

Background: Chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO) present major challenges in health care. Thus, biomarkers to identify disease trajectories and response to treatments to improve the lives of affected individuals warrant great research consideration. The requirements that these biomarkers must fulfil for use as practical clinical tools have not yet been adequately investigated.

Management of patients with seasonal allergic rhinitis: Diagnostic consideration of sensitization to non-frequent pollen allergens.

Background: Diagnosis of pollen allergies is mainly based on test allergens for skin prick testing. In the minimum battery of test inhalant allergens recommended by the Global Allergy and Asthma European Network 10 pollen allergens are included. Complementary other pollen allergens may need to be considered; however, respective awareness may not always be granted.

Immunocompromised Patients with Therapy-Refractory Chronic Skin Diseases Show Reactivation of Latent Epstein‒Barr Virus and Cytomegalovirus Infection.

Reactivation of latent Epstein‒Barr virus (EBV) and/or Cytomegalovirus (CMV) infection is a dreaded complication in immunocompromised patients receiving hematopoietic stem cell transplantation. Evidence is sparse on whether subclinical reactivation of viral infection may also be of clinical relevance in dermatological patients. We screened patients (N = 206) suffering from chronic skin diseases for subclinical reactivation of EBV and CMV infection.

Keratinocytes Regulate the Threshold of Inflammation by Inhibiting T Cell Effector Functions.

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production.

Anti-ferroptotic mechanism of IL4i1-mediated amino acid metabolism.

Interleukin-4-induced-1 (IL4i1) is an amino acid oxidase secreted from immune cells. Recent observations have suggested that IL4i1 is pro-tumorigenic via unknown mechanisms. As IL4i1 has homologs in snake venoms (L-amino acid oxidases [LAAO]), we used comparative approaches to gain insight into the mechanistic basis of how conserved amino acid oxidases regulate cell fate and function.