Mannose‐Modified Multi‐Walled Carbon Nanotubes as a Delivery Nanovector Optimizing the Antigen Presentation of Dendritic Cells

Dendritic cells (DCs) based cancer immunotherapy is largely dependent on adequate antigen delivery and efficient induction of DCs maturation to produce sufficient antigen presentation and ultimately lead to substantial activation of tumor‐specific CD8+ T cells. Carbon nanotubes (CNTs) have attracted great attention in biomedicine because of their unique physicochemical properties. In order to effectively deliver tumor antigens to DCs and trigger a strong anti‐tumor immune response, herein, a specific DCs target delivery system was assembled by using multi‐walled carbon nanotubes modified with mannose which can specifically bind to the mannose receptor on DCs membrane. Ovalbumin (OVA) as a model antigen, could be adsorbed on the surface of mannose modified multi‐walled carbon nanotubes (Man‐MWCNTs) with a large drug loading content. This nanotube‐antigen complex showed low cytotoxicity to DCs and was efficiently engulfed by DCs to induce DCs maturation and cytokine release in vitro, indicating that it could be a potent antigen‐adjuvant nanovector of efficient antigen delivery for therapeutic purpose.Perfectly delivered! Mannose‐modified multi‐walled carbon nanotubes (Man‐MWCNTs) could efficiently deliver a large amount of antigen to bone marrow derived dendritic cells (DCs) through ligand/receptor interactions of mannose, inducing enhanced BMDCs maturation and cytokines secretion.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/1/open201900126-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/2/open201900126.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/3/open201900126_am.pd

IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients

ObjectiveTo investigate the role of IL-2 in the balance of Th17 and Tregs and elucidate the underlying mechanisms of enhanced Th17 differentiation in primary Sjögren’s syndrome (pSS) patients.MethodsThis study involved 31 pSS patients, 7 Sicca patients, and 31 healthy subjects. Th17 and Treg cells were determined by flow cytometry, and IL-17A was detected by immunohistochemistry. IL-2 and IL-6 levels were assessed by ELISA and qPCR. p-STAT5 and p-STAT3 in salivary glands (SGs) were evaluated by immunohistochemistry and flow cytometry. The binding of STAT5 and STAT3 to the Il17a gene locus was measured by chromatin immunoprecipitation.ResultsWe found that the percentage of Th17 cells was increased in the periphery and SG of pSS patients when compared with healthy subjects, but the Treg cells was unchanged. Meanwhile, the IL-2 level was reduced, and the IL-6 and IL-17A level was increased in the plasma of pSS patients. The ratio of IL-2 and IL-6 level was also decreased and IL-2 level was negatively correlated with the level of IL-17A. The expression of Il6 and Il17a mRNA was significantly increased, whereas Foxp3, Tgfb1, Tnfa, and Ifng mRNA were comparable. Furthermore, the level of STAT5 phosphorylation (p-STAT5) was reduced and p-STAT3 was enhanced in the SGs and in peripheral CD4+ T cells of pSS patients. In vitro IL-2 treatment-induced STAT5 competed with STAT3 binding in human Il17a locus, leading to decreased Th17 differentiation, which was associated with the reduced transcription activation marker H3K4me3.ConclusionOur findings demonstrated a Treg-independent upregulation of Th17 generation in pSS, which is likely due to a lack of IL-2-mediated suppression of Th17 differentiation. This study identified a novel mechanism of IL-2-mediated immune suppression in pSS

Similar Transition Processes in Synovial Fibroblasts from Rheumatoid Arthritis and Osteoarthritis: A Single-Cell Study

Rheumatoid arthritis (RA) and osteoarthritis (OA) are common rheumatic disorders that primarily involve joints. The inflammation of the synovium can be observed in both of the two diseases. Synovial fibroblasts (SFs) play an important role in the inflammatory process of the synovium. The functional states of synovial fibroblasts are heterogeneous, and the detailed transition process of their functional states is still unclear. By using transcriptomic data of SFs at a single-cell level, we found a similar transition process for SFs in RA and OA. We also identified the potential regulatory effects of the WNT signaling pathway, the TGF-β signaling pathway, the FcεRI signaling pathway, and the ERBB signaling pathway on modifying the SFs’ functional state. These findings indicate potentially overlapped pathogenic mechanisms in these two diseases, which may help uncover new therapeutic targets to ameliorate disease progression

The Increased Ratio of Blood CD56bright NK to CD56dim NK Is a Distinguishing Feature of Primary Sjögren’s Syndrome

Objective. The aim of this study was to characterize the subsets of circulating CD56+ NK cells in pSS patients and their potential value in the diagnosis and/or prediction of prognosis in patients with pSS. Methods. We included 52 pSS patients fulfilling the 2002 AECG criteria or 2012 ACR criteria and 20 age- and gender-matched healthy volunteers. The frequency and absolute number of NK cells and CD56 NK cell subsets in peripheral blood samples were detected by flow cytometry. Other laboratory parameters such as the IgG level and complement protein levels were extracted from the clinical system. Results. Both the frequency and the absolute number of peripheral blood NK cells were reduced in pSS patients compared to healthy controls. The proportion of CD56bright NK cell subset was increased, and the proportion of CD56dim NK cell subset was decreased among NK cells, resulting in the ratio of CD56bright NK to CD56dim NK which was significantly elevated in pSS patients. ROC analysis indicated that the AUC of CD56bright NK/CD56dim NK ratio was 0.838, and the best diagnostic cut-off point was 0.0487 for pSS patients. Furthermore, this CD56bright NK/CD56dim NK ratio was positively correlated with the IgG level and negatively correlated with the complement protein C3 and C4 levels. More importantly, the CD56bright/CD56dim NK ratio was either slightly increased or not changed in other autoimmune diseases such as SLE and IgG4-related disease. Conclusion. Our findings suggest that the ratio of blood CD56bright NK to CD56dim NK might have a diagnostic value relatively specific for pSS

High-flow nasal cannula oxygen therapy versus noninvasive ventilation for patients with blunt chest trauma: protocol for a randomized controlled trial

Abstract Background High-flow nasal cannula oxygen therapy (HFNC) is recommended by some scholars as an optimized respiratory support method for blunt chest trauma (BCT) patients. The basis of this recommendation is limited, however, and the efficacy of HFNC or noninvasive ventilation (NIV) in BCT patients has not yet been rigorously explored. This study aims to determine if HFNC is non-inferior to NIV in reducing treatment failure in moderate to severe BCT patients with acute respiratory failure. Methods This will be a prospective, open-label, multicenter, non-inferiority, randomized controlled trial. Moderate to severe BCT patients with acute respiratory failure (100mmHg < PaO2/FiO2 ≦ 200mmHg) who do not need immediate intubation will be randomized to HFNC or NIV within 48 h after trauma. The primary outcome is treatment failure, defined as invasive ventilation or a switch in respiratory support modality (from HFNC to NIV or vice-versa). Secondary outcomes include arterial blood gas analysis and vital signs at 2 and 12 h after initiating HFNC or NIV treatment, as well as patients’ comfort scores, dyspnea scores, daily number of nursing airway care interventions, incidence of pneumonia or pneumothorax, facial skin breakdown, duration of NIV or HFNC, 28-day mortality, and total ICU and hospital lengths of stay. Based on an α error of 5% and a β error of 80%, with a non-inferiority limit of 9%, a sample size of 562 will be required to accomplish the trial goal, considering potential patient dropouts and nonparametric analysis. Discussion We hypothesize that HFNC will be non-inferior to NIV in reducing treatment failure in moderate to severe BCT with acute respiratory failure. The results should be useful for judging whether HFNC could be an effective alternative to NIV to treat moderate to severe BCT patients, especially for those who do not tolerate or have contraindications for NIV. Trial registration Chinese Clinical Trial Registry ChiCTR1800017313 . Registered on July 24, 2018