Search

Background: many genes associated with asthma explain only a fraction of its heritability. Most genome-wide association studies (GWASs) used a broad definition of 'doctor-diagnosed asthma', thereby diluting genetic signals by not considering asthma heterogeneity. The objective of our study was to identify genetic associates of childhood wheezing phenotypes.Methods: we conducted a novel multivariate GWAS meta-analysis of wheezing phenotypes jointly derived using unbiased analysis of data collected from birth to 18 years in 9,568 individuals from five UK birth-cohorts.Results: 44 independent SNPs were associated with early-onset persistent, 25 with preschool remitting, 33 with mid-childhood remitting and 32 with late-onset wheeze. We identified a novel locus on chr9q21.13 (close to annexin 1 (ANXA1), pConclusions: targeting this pathway in persistent disease may represent an exciting therapeutic prospect.

This is the final version of The Guide to Conscious Editing for Wilson Special Collections Library. The work was created by the Conscious Editing Steering Committee for the University Libraries of the University of North Carolina at Chapel Hill. Between September 2019 and April 2022, more than twenty archivists, librarians, and humanities scholars contributed to the Guide.

As part of the University Libraries Reckoning Initiative, Library staff engaged in a voluntary 21-Day Racial Equity Challenge to further skills around understanding racism, bias, and racial inequity. The University Libraries 21-Day Racial Equity Challenge inspired participants to engage, act, and reflect on race and racial equity in personal spaces as well as in the organization and the profession.

From October 2017 through January 2019, the North Carolina Digital Heritage Center (NCDHC) undertook a content management system migration of over 44,000 library digital collection objects, comprising over 2 million individual files of varying types and their associated metadata, produced over a ten-year period. This case study describes NCDHC’s experience evaluating potential systems, navigating vendor relationships, exporting and improving data, migration logistics, adapting existing workflows, and communicating with stakeholders.

Background Although originally defined as a type 2 (T2) immune-mediated condition, non-T2 cytokines, such as IFN-γ and IL-17A, have been implicated in asthma pathogenesis, particularly in patients with severe disease. IL-10 regulates TH cell phenotypes and can dampen T2 immunity to allergens, but its functions in controlling non-T2 cytokine responses in asthmatic patients are unclear. Objective We sought to determine how IL-10 regulates the balance of TH cell responses to inhaled allergen. Methods Allergic airway disease was induced in wild-type, IL-10 reporter, and conditional IL-10 or IL-10 receptor α (IL-10Rα) knockout mice by means of repeated intranasal administration of house dust mite (HDM). IL-10 and IFN-γ signaling were disrupted by using blocking antibodies. Results Repeated HDM inhalation induced a mixed IL-13/IL-17A response and accumulation of IL-10–producing forkhead box P3–negative effector CD4+ T cells in the lungs. Ablation of T cell–derived IL-10 increased the IFN-γ and IL-17A response to HDM, reducing IL-13 levels and airway eosinophilia without affecting IgE levels or airway hyperresponsiveness. The increased IFN-γ response could be recapitulated by IL-10Rα deletion in CD11c+ myeloid cells or local IL-10Rα blockade. Disruption of the T cell–myeloid IL-10 axis resulted in increased pulmonary monocyte–derived dendritic cell numbers and increased IFN-γ–dependent expression of CXCR3 ligands by airway macrophages, which is suggestive of a feedforward loop of TH1 cell recruitment. Augmented IFN-γ responses in the HDM allergic airway disease model were accompanied by increased disruption of airway epithelium, which was reversed by therapeutic blockade of IFN-γ. Conclusions IL-10 from effector T cells signals to CD11c+ myeloid cells to suppress an atypical and pathogenic IFN-γ response to inhaled HDM., Graphical abstract