Cells bend their plasma membranes into highly curved forms to interact with the local environment, but how shape generation is regulated is not fully resolved. Here, we report a synergy between shape-generating processes in the cell interior and the external organization and composition of the cell-surface glycocalyx. Mucin biopolymers and long-chain polysaccharides within the glycocalyx can generate entropic forces that favor or disfavor the projection of spherical and finger-like extensions from the cell surface. A polymer brush model of the glycocalyx successfully predicts the effects of polymer size and cell-surface density on membrane morphologies. Specific glycocalyx compositions can also induce plasma membrane instabilities to generate more exotic undulating and pearled membrane structures and drive secretion of extracellular vesicles. Together, our results suggest a fundamental role for the glycocalyx in regulating curved membrane features that serve in communication between cells and with the extracellular matrix. (A) The native and synthetic mucin biopolymers that were genetically encoded and used throughout this work. (B) Quantification of membrane tube density in epithelial cells. Mucin polymers induce dramatic tubularization compared to wild-type (Control) cells and compared to a similarly sized biopolymer composed of EGF-like repeats from Notch1 and the Muc1 transmembrane anchor with GFP reporter (EGF-repeats GFP-DCT) cells. Number of cells analyzed is shown on the x axis for each condition. Box notches here and elsewhere indicate 95% confidence intervals. The number of tandem repeats (TRs) are indicated in Muc1 constructs. (C) Scanning electron microscopy (SEM) images of cells expressing the indicated biopolymer. (D) Labelled glycans and membrane morphologies resolved with single-molecule localization microscopy in Muc1-42TR DCT-expressing cells before and after mucin backbone digestion with the StcE mucinase. Images are shown as 2D color-coded histograms of localizations with 32 nm bin width. (E) Representative confocal images of GUVs with and without anchorage of recombinant Podocalyxin. (F) (Left) Cartoons of Muc1 GFP-DCT polymers of varying length. (Right) Flow cytometry data showing similar cell-surface expression levels of the mucins using a GFP-binding nanobody, n = 3, >40,000 cells per population. (G) Representative SEM images of cells expressing mucins with a varying number of TRs. (H) Quantification of membrane tube density for cells expressing the indicated mucins, significance compared to 42TR. ***p < 0.001; ns, not significant (post-hoc Student's two-tailed t test). See also Figure S1.

Transforming growth factor-β (TGF-β) signaling in naive T cells induces expression of the transcription factor Foxp3, a 'master' regulator of regulatory T cells (T reg cells). However, the molecular mechanisms leading to Foxp3 induction remain unclear. Here we show that Itch −/− T cells were resistant to TGF-β treatment and had less Foxp3 expression. The E3 ubiquitin ligase Itch associated with and promoted conjugation of ubiquitin to the transcription factor TIEG1. Itch cooperated with TIEG1 to induce Foxp3 expression, which was reversed by TIEG1 deficiency. Functionally, 'TGF-β-converted' T reg cells generated from TIEG1-deficient mice were unable to suppress airway inflammation in vivo. These results suggest TIEG and Itch contribute to a ubiquitindependent nonproteolytic pathway that regulates inducible Foxp3 expression and the control of allergic responses.Allergic asthma is a chronic inflammatory disease of the airways characterized by higher serum immunoglobulin E (IgE) concentrations, airway hyper-responsiveness, excessive airway mucus production, lung eosinophilia and airway remodeling. Differentiation of CD4 + T cells into T helper type 2 (T H 2) cells renders them able to produce the cytokines interleukin 4 (IL-4), IL-5 and IL-13, which are critical for driving asthmatic pathogenesis 1,2 . The induction of T H 2 differentiation is regulated by many factors, including the properties of the antigens, the duration of stimulation, and genetic factors. In addition, the T H 2-mediated immune responses are counterbalanced by tolerogenic mechanisms that prevent excessive reactions. One of the tolerance mechanisms involves regulatory T cells (T reg cells), which limit allergic responses 3 . In mouse models of allergic asthma, repeated delivery of antigen to the respiratory tract results in inhibition of allergic responses to the same antigen after subsequent challenges 4 . Published studies have shown that repeated treatment with a low dose of antigen induces the generation of Foxp3 + CD4 + CD25 + T reg cell population, which accounts for the attenuation of T H 2-mediated airway inflammation 5,6 . T reg cells represent a unique subpopulation of CD4 + T cells that suppress the effector function of other types of T cells and

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BackgroundDry eye disease (DED) is one of the most prevalent ocular diseases in the world. In China, new lifestyles driven by information technology and the rapid ageing process have brought DED a severe public health concern. The aim of our study was to obtain the pooled prevalence of DED in China and explore its potential correlates.MethodsA comprehensive systematic review was conducted to identify all relevant literature published since 1990. Meta-analysis and meta-regression approaches were adopted to estimate the prevalence of DED. The number of people with DED was obtained by multiplying the corresponding demographic data in 2010.ResultsAdvanced age, female sex and larger latitude were significant risk factors for DED by symptoms and signs, whereas only advanced age was positively associated with an increased prevalence of DED by symptoms. In 2010, the prevalence of DED by symptoms and signs were 13.55% (95% CI = 10.00-18.05) and that of DED by symptoms was 31.40% (95% CI = 23.02-41.13) in Chinese people aged 5-89 years, corresponding to a total of 170.09 million (95% CI = 125.52-226.63) and 394.13 million (95% CI = 288.99-516.30) affected individuals respectively.ConclusionsThe huge burden of DED in China calls for more public health attention and actions. Improved epidemiological studies on DED prevalence are still urgently needed.

Human body surfaces, such as the skin, intestines, and respiratory and urogenital tracts, are colonized by a large number of microorganisms, including bacteria, fungi, and viruses, with the gut being the most densely and extensively colonized organ. The microbiome plays an essential role in immune system development and tissue homeostasis. Gut microbiota dysbiosis not only modulates the immune responses of the gastrointestinal (GI) tract but also impacts the immunity of distal organs, such as the lung, further affecting lung health and respiratory diseases. Here, we review the recent evidence of the correlations and underlying mechanisms of the relationship between the gut microbiota and common respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), lung cancer, and respiratory infection, and probiotic development as a therapeutic intervention for these diseases.