Bertramwheeler5035

We further demonstrate that both IL-4- and Combo-CD40-B cells are efficient in promoting T cell activation and proliferation compared with IL-21-CD40-B cells. Thus, our study provides a better appreciation of CD40-B cell plasticity and biology. In addition, the stimulation of B cells with CD40L, IL-4, and IL-21 allows for the fast generation of high numbers of efficient APC, therefore providing a prospective tool for research and clinical applications such as cancer immunotherapy.Gut microbiota is increasingly linked to the development of various pulmonary diseases through a gut-lung axis. However, the mechanisms by which gut commensal microbes impact trafficking and functional transition of immune cells remain largely unknown. Using integrated microbiota dysbiosis approaches, we uncover that the gut microbiota directs the migration of group 2 innate lymphoid cells (ILC2s) from the gut to the lung through a gut-lung axis. We identify Proteobacteria as a critical species in the gut microbiome to facilitate natural ILC2 migration, and increased Proteobacteria induces IL-33 production. Mechanistically, IL-33-CXCL16 signaling promotes the natural ILC2 accumulation in the lung, whereas IL-25-CCL25 signals augment inflammatory ILC2 accumulation in the intestines upon abdominal infection, parabiosis, and cecum ligation and puncture in mice. We reveal that these two types of ILC2s play critical but distinct roles in regulating inflammation, leading to balanced host defense against infection. Overall results delineate that Proteobacteria in gut microbiota modulates ILC2 directional migration to the lung for host defense via regulation of select cytokines (IL-33), suggesting novel therapeutic strategies to control infectious diseases.Macrophages play a central role in lung physiology and pathology. In this study, we show in mice that alveolar macrophages (AMs), unlike other macrophage types (interstitial, peritoneal, and splenic macrophages), constitutively express programmed death-1 ligand 1 (PD-L1), thereby possessing a superior phagocytic ability and the capacity to repress CTLs by cis- and trans-interacting with CD80 and programmed death-1 (PD-1), respectively. This extraordinary ability of AMs assures optimal protective immunity and tolerance within the lung. These findings uncover a unique characteristic of AMs and an innate immune function of PD-L1 and CD80 and therefore help in the understanding of lung physiology, diseases, and PD-L1/PD-1-based immunotherapy.The transcriptional repressor Bcl6 has been reported as required for development of a subset of classical dendritic cell (cDCs) called cDC1, which is responsible for cross-presentation. However, mechanisms and in vivo functional analysis have been lacking. We generated a system for conditional deletion of Bcl6 in mouse cDCs. We confirmed the reported in vitro requirement for Bcl6 in cDC1 development and the general role for Bcl6 in cDC development in competitive settings. However, deletion of Bcl6 did not abrogate the in vivo development of cDC1. Instead, Bcl6 deficiency caused only a selective reduction in CD8α expression by cDC1 without affecting XCR1 or CD24 expression. Selleck VB124 Normal cDC1 development was confirmed in Bcl6cKO mice by development of XCR1+ Zbtb46-GFP+ cDC1 by rejection of syngeneic tumors and by priming of tumor-specific CD8 T cells. In summary, Bcl6 regulates a subset of cDC1-specific markers and is required in vitro but not in vivo for cDC1 development.Insufficient autophagic degradation has been implicated in accelerated cellular senescence during chronic obstructive pulmonary disease (COPD) pathogenesis. Aging-linked and cigarette smoke (CS)-induced functional deterioration of lysosomes may be associated with impaired autophagy. Lysosomal membrane permeabilization (LMP) is indicative of damaged lysosomes. Galectin-3 and tripartite motif protein (TRIM) 16 play a cooperative role in recognizing LMP and inducing lysophagy, a lysosome-selective autophagy, to maintain lysosome function. In this study, we sought to examine the role of TRIM16-mediated lysophagy in regulating CS-induced LMP and cellular senescence during COPD pathogenesis by using human bronchial epithelial cells and lung tissues. CS extract (CSE) induced lysosomal damage via LMP, as detected by galectin-3 accumulation. Autophagy was responsible for modulating LMP and lysosome function during CSE exposure. TRIM16 was involved in CSE-induced lysophagy, with impaired lysophagy associated with lysosomal dysfunction and accelerated cellular senescence. Airway epithelial cells in COPD lungs showed an increase in lipofuscin, aggresome and galectin-3 puncta, reflecting accumulation of lysosomal damage with concomitantly reduced TRIM16 expression levels. Human bronchial epithelial cells isolated from COPD patients showed reduced TRIM16 but increased galectin-3, and a negative correlation between TRIM16 and galectin-3 protein levels was demonstrated. Damaged lysosomes with LMP are accumulated in epithelial cells in COPD lungs, which can be at least partly attributed to impaired TRIM16-mediated lysophagy. Increased LMP in lung epithelial cells may be responsible for COPD pathogenesis through the enhancement of cellular senescence.

Surgical site infection (SSI) is one of the most common complications after gastrointestinal surgery, with a reported incidence of approximately 10%-25%, which is higher than the rates after other types of surgery. Intraoperative wound irrigation (IOWI) is a simple intervention for SSI prevention, and recent studies have reported that IOWI with aqueous povidone-iodine (PVP-I) is significantly more effective at reducing the incidence of SSI than saline. However, the evidence level of previous trials evaluating the efficacy of aqueous PVP-I solution for preventing SSI has been low.

We propose a single-institute, prospective, randomised, blinded-endpoint trial to assess the superiority of IOWI with aqueous 10% PVP-I solution compared with normal saline for reducing SSI in clean-contaminated wounds after elective gastrointestinal surgery. In the study group, IOWI with 40 mL of aqueous 10% PVP-I solution is performed for 1 min before skin suture, and in the control group, IOWI with 100 mL of saline is performed for 1 min before skin suture.