Biology subjects

Jin, J.

Publications and source records attributed to Jin, J..

At least 163 records · Page 9Linked to original sources

bioRxiv2020

Polygenic Risk Scores for Kidney Function to the Circulating Proteome, and Incident Kidney Diseases: the Atherosclerosis Risk in Communities Study

Genome-wide association studies (GWAS) have revealed numerous loci for kidney function (estimated glomerular filtration rate, eGFR). The relationship of polygenic predictors of eGFR, risk of incident adverse kidney outcomes, and the plasma proteome is not known. We developed a genome-wide polygenic risk score (PRS) using a weighted average of 1.2 million SNPs for eGFR using the LDpred algorithm, summary statistics generated by a European-ancestry (EA) meta-analysis of the CKDGen Consortium (N=558,423) and UK Biobank GWAS for eGFR (90% of the cohort; N=289,432), followed by best parameter selection using data from the remaining 10% of the UK Biobank (N=32,159). We then tested the association of the PRS among 8,886 EA participants in the Atherosclerosis Risk in Communities (ARIC) study (mean age: 54{+/-}6 years, 53% female) with incident chronic kidney disease (CKD), end stage kidney disease (ESKD), kidney failure (KF), and acute kidney injury (AKI). We also examined 4,877 plasma proteins measured at two time points (visit 3 (1993-95) and visit 5 (2011-13)) in relation to the PRS and compared associations between the proteome and eGFR itself. All models were adjusted for age, sex, center, and the first 10 principal components of ancestry. The developed PRS had an R2 for eGFR of 0.07 in ARIC. Over 30 years of follow up, the number of incident CKD, ESKD, KF, and AKI were 2,959, 137, 470, and 1,723, respectively. The PRS showed significant associations with all outcomes: hazard ratios (95% CI) per 1 SD lower PRS were 1.33 (1.28, 1.39), 1.20 (1.00, 1.42), 1.17 (1.06, 1.28), and 1.07 (1.02, 1.12) for incident CKD, ESKD, KF, and AKI respectively. The PRS was significantly associated (Bonferroni threshold P<1.02 x 10-5) with 108 proteins at both time points. The strongest associations were with cystatin-C (a marker of kidney function used in clinical practice), collagen alpha-1 (XV) chain, and desmocollin-2. All significant correlations with the PRS were negative, except those of testican-2 and angiostatin. Correlations of proteins with eGFR were much stronger than those with the PRS. Overall, we demonstrated that the PRS for eGFR is now sufficiently strong to capture risk for a spectrum of incident kidney diseases as well as broadly influence the plasma proteome.

genetics↗

bioRxiv2020

Designed Variants of Recombinant ACE2-Fc that Decouple Anti-SARS-CoV-2 Activities from Unwanted Cardiovascular Effects

Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for SARS-CoV-2, and recombinant ACE2 decoys are being evaluated as new antiviral therapies. We designed and tested an antibody-like ACE2-Fc fusion protein, which has the benefit of long pharmacological half-life and the potential to facilitate immune clearance of the virus. Out of a concern that the intrinsic catalytic activity of ACE2 may unintentionally alter the balance of its hormonal substrates and cause adverse cardiovascular effects in treatment, we performed a mutagenesis screening for inactivating the enzyme. Three mutants, R273A, H378A and E402A, completely lost their enzymatic activity for either surrogate or physiological substrates. All of them remained capable of binding SARS-CoV-2 and could suppress the transduction of a pseudotyped virus in cell culture. This study established new ACE2-Fc candidates as antiviral treatment for SARS-CoV-2 without potentially harmful side effects from ACE2s catalytic actions toward its vasoactive substrates.

biochemistry↗

bioRxiv2020

A 3.4-A cryo-EM structure of the human coronavirus spike trimer computationally derived from vitrified NL63 virus particles

Human coronavirus NL63 (HCoV-NL63) is an enveloped pathogen of the family Coronaviridae that spreads worldwide and causes up to 10% of all annual respiratory diseases. HCoV-NL63 is typically associated with mild upper respiratory symptoms in children, elderly and immunocompromised individuals. It has also been shown to cause severe lower respiratory illness. NL63 shares ACE2 as a receptor for viral entry with SARS-CoV and SARS-CoV-2. Here we present the in situ structure of HCoV-NL63 spike (S) trimer at 3.4-[A] resolution by single-particle cryo-EM imaging of vitrified virions without chemical fixative. It is structurally homologous to that obtained previously from the biochemically purified ectodomain of HCoV-NL63 S trimer, which displays a 3-fold symmetric trimer in a single conformation. In addition to previously proposed and observed glycosylation sites, our map shows density at other amino acid positions as well as differences in glycan structures. The domain arrangement within a protomer is strikingly different from that of the SARS-CoV-2 S and may explain their different requirements for activating binding to the receptor. This structure provides the basis for future studies of spike proteins with receptors, antibodies, or drugs, in the native state of the coronavirus particles.

biophysics↗

bioRxiv2020

The validation of new phase-dependent gait stability measures: a modeling approach

Identification of individuals at risk of falling is important when designing fall prevention methods. Current measures that estimate gait stability and robustness appear limited in predicting falls in older adults. Inspired by recent findings on changes in phase-dependent local stability within a gait cycle, we devised several phase-dependent stability measures and tested for their usefulness to predict gait robustness in compass walker models. These measures are closely related to the often-employed maximum finite-time Lyapunov exponent and maximum Floquet multiplier that both assess a systems response to infinitesimal perturbations. As such, they entail linearizing the system but this is realized in a rotating hypersurface orthogonal to the period-one solution followed by estimating the trajectory-normal divergence rate of the swing phases and the foot strikes. We correlated the measures with gait robustness, i.e. the largest perturbation a walker can handle, in two compass walker models with either point or circular feet to estimate their prediction accuracy. To also test for the dependence of the measures under state space transform, we represented the point-feet walker in both Euler-Lagrange and Hamiltonian canonical form. Our simulations revealed that for most of the measures their correlation with gait robustness differs between models and between different state space forms. In particular the latter may jeopardize many stability measures predictive capacity for gait robustness. The only exception that consistently displayed strong correlations is the divergence of foot strike. Our results admit challenges of using phase-dependent stability measures as objective means to estimate the risk of falling.

bioengineering↗

bioRxiv2020

Atomic-scale Characterization of Mature HIV-1 Capsid Stabilization by Inositol Hexakisphosphate (IP6)

Inositol hexakisphosphates (IP6) are cellular cofactors that promote the assembly of mature capsids of the human immunodeficiency virus (HIV). These negatively charged molecules coordinate an electropositive ring of arginines at the center of pores distributed throughout the capsid surface. Kinetic studies indicate that the binding of IP6 increases the stable life times of the capsid by several orders of magnitude from minutes to hours. Using all-atom molecular dynamics simulations, we uncover the mechanisms that underlie the unusually high stability of mature capsids in complex with IP6. We find that capsid hexamers and pentamers have differential binding modes for IP6. Ligand density calculations show three sites of interaction with IP6 including at a known capsid-inhibitor binding pocket. Free energy calculations demonstrate that IP6 preferentially stabilizes pentamers over hexamers to enhance fullerene modes of assembly. These results elucidate the molecular role of IP6 in stabilizing and assembling the retroviral capsid.

biophysics↗

bioRxiv2020

Establishment of a stable transgenic g6pdM1315-1443 zebrafish line with glucose-6-phosphate dehydrogenase deficiency

ABSTRACTGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzymopathy in humans and is associated with a predisposition to hemolysis. However, there are few animal models to that adequately mimic associated human disease states that could be used to evaluate strategies to address clinical syndromes attributable to G6PD deficiency. In the present study, we aimed to establish a stable transgenic zebrafish model of G6PD deficiency that recapitulates the clinical manifestations of G6PD deficiency. We incorporated a stable transgene of G6PD lacking nucleotides from 1315 to 1443 denoted Tg(zgata1:g6pdM1315-1443-egfp). Functional analysis showed that Tg(zgata1:g6pdM1315-1443-egfp) transgenic zebrafish demonstrate a decrease in g6pd activity, reduced GSH levels and hemoglobin content, and increases in pericardial edema in response to α-naphthol exposure, similar to human subjects with G6PD deficiency. We detected no other significant phenotypic abnormalities compared to controls. Taken together, these observations indicate that the Tg(zgata1:g6pdM1315-1443-egfp) zebrafish line mirrors key clinical manifestations of G6PD deficiency in humans. This model may facilitate mechanistic studies and promote translational research related to G6PD deficiency.Competing Interest StatementThe authors have declared no competing interest.View Full Text

zoology↗

bioRxiv2020

Establishment of a stable zg6pdM118-144 transgenic zebrafish model of glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common genetic defect and enzymopathy with a wide distribution and increased public health concern, predisposes subjects succumb to oxidative stress. G6PD deficiency has been associated with hemolysis. Clinically, G6PD deficiency is asymptomatic and the clinical manifestations occur with the exposure to certain agents. Due to the lack of suitable animal models that can predict the clinical hemolytic potential of drugs, it needs an appropriate research model to fully recapitulate the manifestations of G6PD deficiency in clinic, to optimize the malaria therapy and promote anti-malarias development. The present study has displayed a stable transgenic Tg(zgata1-g6pdM118-144-egfp) zebrafish model with G6PD deficiency which mimics the clinical features of G6PD deficiency phenotypically and functionally. The findings showed that there was an inadequate level of reduced GSH in the transgenic Tg(zgata1-g6pdM118-144-egfp) zebrafish line in the presence or absence of α-naphthol, compared to the wildtype zebrafish, indicating an attenuation of g6pd activity in the transgenic zebrafish line. In addition, the observations show that there is a less abundance of g6pd in the transgenic Tg(zgata1-g6pdM118-144-egfp) zebrafish line. On the other hand, there is no morphological abnormality in the transgenic Tg(zgata1-g6pdM118-144-egfp) zebrafish line. Taken together, our work has delivered a novel stable transgenic zebrafish model of G6PD deficiency that will facilitate the mechanistic and functional elucidation for the role of G6PD in erythrocytic pathophysiology. This model will promote the translational research for the drug development, in particular, for anti-malarias development.Competing Interest StatementThe authors have declared no competing interest.View Full Text

zoology↗

bioRxiv2020

Experimental study of tissue-engineered urethra with collagen / chitosan composite as scaffolds

In this article we investigated the preparation of tissue-engineered urethra by using the urethral epithelial subculture cells of male New Zealand young rabbits. We inoculated the epithelial cells of urinary mucosa of male New Zealand young rabbits on collagen, chitosan and collagen chitosan composite as scaffolds to prepare tissue-engineered urethra. The results of inverted phase contrast microscope, HE staining and scanning electron microscope of three kinds of tissue-engineered urethra were compared. Whats more, we reported a new method for quantitative and rapid detection of epithelial cell activity of urinary mucosa in situ by Interactive Laser Cytometer. The collagen chitosan composite was more similar to the extracellular matrix of mammalian. Its three-dimensional porous structure had a high area volume ratio, which was conducive to cell adhesion, growth and metabolism. In vitro, the urethral epithelial cells had been cultured on collagen chitosan composite, and the tissue-engineered urethra was successfully prepared, which laid a solid foundation for further in vivo experiments.

bioengineering↗

bioRxiv2020

New Soluble Angiopoietin Analog of C4BP-ANG1 Prevents Pathological Vascular Leakage

Vascular leak is a key driver of organ injury in diseases such as Acute Respiratory Distress Syndrome caused by viruses, including COVID-19. Strategies that reduce enhanced permeability and vascular inflammation are promising therapeutic targets. Activation of the Angiopoietin-1 (Angpt1)-Tie2 tyrosine kinase signaling pathway is an important regulator of vascular quiescence. Here we describe the design and construction of a new soluble ANGPT1 mimetic that is a potent activator of endothelial Tie2 in vitro and in vivo. Using a chimeric fusion strategy, we replaced the extracellular matrix (ECM) binding and oligomerization domain of ANGPT1 with a heptameric scaffold derived from the C-terminus of serum complement protein C4-binding protein (C4BP). We refer to this new fusion protein biologic as C4BP-ANG1, which forms a stable heptamer and induces TIE2 phosphorylation in cultured cells, and in the lung following i.v. injection of mice. Injection of C4BP-ANG1 ameliorates VEGF- and lipopolysaccharide-induced vascular leakage, in keeping with the known functions of Angpt1-Tie2 in maintaining quiescent vascular stability, and therefore is a promising candidate treatment for inflammatory endothelial dysfunction.

biochemistry↗

bioRxiv2020

Population sequencing enhances understanding of tea plant evolution

Tea is an economically important plant characterized by a large genome size and high heterozygosity and species diversity. In this study, we assembled a 3.26 Gb high-quality chromosome-scale genome for tea using the Longjing 43 cultivar of Camellia sinensis var. sinensis. Population resequencing of 139 tea accessions from around the world was used to investigate the evolution of tea and to reveal the phylogenetic relationships among tea accessions. With the spread of tea cultivation, hybridization has increased the heterozygosity and wide-ranging gene flow among tea populations. Population genetics and transcriptomics analyses revealed that during domestication, the selection for disease resistance and flavor in C. sinensis var. sinensis populations has been stronger than that in C. sinensis var. assamica populations. The data compiled in this study provide new resources for the marker assisted breeding of tea and are a basis for further research on the genetics and evolution of tea.

genomics↗

bioRxiv2020

Reactive oxygen species as important regulators of cell division

Currently, the role of reactive oxygen species (ROS) in plant growth is a topic of interest. In this study, we discuss the role of ROS in cell division. We analyzed ROS impact on the stiffness of plant cell walls and whether ROS play an important role in Brassica napus ability to adapt to cold stress. Cultivated sterile seedlings and calli of cold-tolerant cultivar 16NTS309 were subjected to cold stress at 25{degrees}C and 4{degrees}C, respectively. Under normal conditions, O2.- mainly accumulated in the leaf edges, shoot apical meristem, leaf primordia, root tips, lateral root primordia, calli of meristematic nodular tissues, cambia, vascular bundles and root primordia, which are characterized by high division rates. After exposure to cold stress, the malondialdehyde and ROS (O2.-) contents in roots, stems and leaves of cultivar 16NTS309 were significantly higher than under non-cold conditions (P < 0.05). ROS (O2.-) were not only distributed in these zones, but also in other cells, at higher levels than under normal conditions. A strong ROS-based staining appeared in the cell wall. The results support a dual role for apoplastic ROS, in which they have direct effects on the stiffness of the cell wall, because ROS cleave cell-wall, and act as wall loosening agents, thereby either promoting or restricting cellular division. This promotes the appearance of new shoots and a strong root system, allowing plants to adapt to cold stress.

plant biology↗

bioRxiv2020

Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche

BackgroundMuscle stem cells (MuSCs) are requisite for skeletal muscle regeneration and homeostasis. Proper functioning of MuSCs, including activation, proliferation, and fate decision, is determined by an orchestrated series of events and communication between MuSCs and their niche consisting of the host myofiber and neighbouring cells. A multitude of biochemical stimuli are known to regulate fate and function of MuSCs. However, in addition to biochemical factors, it is conceivable that MuSCs residing between basal lamina and sarcolemma of myofibers are subjected to mechanical forces during muscle stretch-shortening cycles due to myofascial connections between MuSCs and myofibers. MuSCs have been shown to respond to mechanical forces in vitro but it remains to be proven whether physical forces are also exerted on MuSCs in their native niche and whether they contribute to the functioning and fate of MuSCs. MethodsMuSCs deformation in their native niche resulting from mechanical loading of ex vivo myofiber bundles were visualized utilizing mT/mG double-fluorescent Cre-reporter mouse and multiphoton microscopy. MuSCs were subjected to 1 hour pulsating fluid shear stress with a peak shear stress rate of 8.8 Pa/s. After treatment, nitric oxide and mRNA expression levels of genes involved in regulation of MuSC proliferation and differentiation were determined. ResultsEx vivo stretching of extensor digitorum longus and soleus myofiber bundles caused compression as well as tensile and shear deformation of MuSCs in their niche. MuSCs responded to pulsating fluid shear stress in vitro with increased nitric oxide production and an upward trend in iNOS mRNA levels, while nNOS expression was unaltered. Pulsating fluid shear stress enhanced gene expression of c-Fos, Cdk4, and IL-6, while expression of Wnt1, MyoD, Myog, Wnt5a, COX2, Rspo1, Vangl2, Wnt10b, and MGF remained unchanged. ConclusionsWe conclude that MuSCs in their native niche are subjected to force-induced deformations due to myofiber stretch-shortening. Moreover, MuSCs are mechanoresponsive as evident by pulsating fluid shear stress-mediated expression of factors by MuSCs known to promote proliferation.

cell biology↗

bioRxiv2019

Deschloroclozapine: a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys

The chemogenetic technology Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) affords remotely reversible control of cellular signaling, neuronal activity and behavior. Although the combination of muscarinic-based DREADDs with clozapine-N-oxide (CNO) has been widely used, sluggish kinetics, metabolic liabilities, and potential off-target effects of CNO represent areas for improvement. Here we provide a new high affinity and selective agonist deschloroclozapine (DCZ) for muscarinic-based DREADDs. Positron emission tomography revealed that DCZ selectively bound to and occupied DREADDs in both mice and monkeys. Systemic delivery of low doses of DCZ (1 or 3 g/kg) enhanced neuronal activity via hM3Dq within minutes in mice and monkeys. Intramuscular injections of DCZ (100 g/kg) reversibly induced spatial working memory deficits in monkeys expressing hM4Di in the prefrontal cortex. DCZ represents the most potent, selective, metabolically stable and fast-acting DREADD agonist reported with utility in both mice and non-human primates for a variety of applications.

neuroscience↗

bioRxiv2019

Deep convolutional neural network and attention mechanism based pan-specific model for interpretable MHC-I peptide binding prediction

Accurate prediction of peptide binding affinity to the major histocompatibility complex (MHC) proteins has the potential to design better therapeutic vaccines. Previous work has shown that pan-specific prediction algorithms can achieve better prediction performance than other approaches. However, most of the top algorithms are neural networks based black box models. Here, we propose DeepAttentionPan, an improved pan-specific model, based on convolutional neural networks and attention mechanisms for more flexible, stable and interpretable MHC-I binding prediction. With the attention mechanism, our ensemble model consisting of 20 trained networks achieves high and more stabilized prediction performance. Extensive tests on IEDBs weekly benchmark dataset show that our method achieves state-of-the-art prediction performance on 21 test allele datasets. Analysis of the peptide positional attention weights learned by our model demonstrates its capability to capture critical binding positions of the peptides, which leads to mechanistic understanding of MHC-peptide binding with high alignment with experimentally verified results. Furthermore, we show that with transfer learning, our pan model can be fine-tuned for alleles with few samples to achieve additional performance improvement. DeepAttentionPan is freely available as an open source software at https://github.com/jjin49/DeepAttentionPan.\n\nAuthor summaryHuman leukocyte antigen (HLA) proteins are classes of proteins that are responsible for immune system regulation in humans. The peptides are short chains of amino acids. HLA class I group present peptides from inside the cell to the cell surface for scrutiny by T cell receptors. For instance, if the cell is infected by a virus, the HLA system will bind to the peptides derived from viral proteins and bring them to the surface of the cell so that the cell can be destroyed by the immune system. Since the HLA genes exhibit extensive polymorphism, there are many HLA alleles binding to different peptides. And this diversity represents challenges in predicting binders for different HLA alleles, which are important in vaccine designs and characterization of immune responses. Before computational algorithms are used to predict the binding relationships of HLA-peptide pairs, scientists need to conduct costly biological experiments to do preliminary screening among a number of peptides and need to use mutant experiments to identify key peptide positions that contribute to the binding. While previous computational methods have been proposed to predict the binding affinity, identifying the binding anchors is not well addressed. Here we developed a deep neural network models with the attention mechanism to learn the binding relationships automatically in an end-to-end way. Our models are able to identify the important binding positions of the peptide sequence by learning the positional importance distribution, which used to be studied a lot only through costly experimental methods. Our model thus not only improves the performance of binding affinity prediction but also allows us to gain biological insight of binding motifs of different alleles via interpreting the learned deep neural network models.

bioinformatics↗

bioRxiv2019

DeepSeqPanII: an interpretable recurrent neural network model with attention mechanism for peptide-HLA class II binding prediction

Human leukocyte antigen (HLA) complex molecules play an essential role in immune interactions by presenting peptides on the cell surface to T cells. With significant progress in deep learning, a series of neural network based models have been proposed and demonstrated with their good performances for peptide-HLA class I binding prediction. However, there still lack effective binding prediction models for HLA class II protein binding with peptides due to its inherent challenges. In this work, we present a novel sequence-based pan-specific neural network structure, DeepSeaPanII, for peptide-HLA class II binding prediction. Compared with existing pan-specific models, our model is an end-to-end neural network model without the need for pre- or post-processing on input samples. Besides state-of-the-art peformance in binding affinity prediction, DeepSeqPanII can also extract biological insight on the binding mechanism over the peptide and HLA sequences by its attention mechanism based binding core prediction capability. The leave-one-allele-out cross validation and benchmark evaluation results show that our proposed network model achieved state-of-the-art performance in HLA-II peptide binding. The source code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPanII.

bioinformatics↗

bioRxiv2019

Molecular Networks and Key Regulators of the Dysregulated Neuronal System in Alzheimer’s Disease

To study the molecular mechanisms driving the pathogenesis and identify novel therapeutic targets of late onset Alzheimers Disease (LOAD), we performed an integrative network analysis of whole-genome DNA and RNA sequencing profiling of four cortical areas, including the parahippocampal gyrus, across 364 donors spanning the full spectrum of LOAD-related cognitive and neuropathological disease severities. Our analyses revealed thousands of molecular changes and uncovered for the first-time multiple neuron specific gene subnetworks most dysregulated in LOAD. ATP6V1A, a critical subunit of vacuolar-type H+-ATPase (v-ATPase), was predicted to be a key regulator of one neuronal subnetwork and its role in disease-related processes was evaluated through CRISPR-based manipulation of human induced pluripotent stem cell derived neurons and RNAi-based knockdown in transgenic Drosophila models. This study advances our understanding of LOAD pathogenesis by providing the global landscape and detailed circuits of complex molecular interactions and regulations in several key brain regions affected by LOAD and the resulting network models provide a blueprint for developing next generation therapeutics against LOAD.

neuroscience↗

bioRxiv2019

Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma

Multiple myeloma (MM) is a malignancy of plasma cells that largely remains incurable. The search for new therapeutic targets is therefore essential. Here we show that a higher expression of the lysine methyltransferase SETD8, which is responsible for histone H4K20 mono-methylation, is an adverse prognosis factor associated with a poor outcome in two cohorts of newly diagnosed patients. Remarkably, primary malignant plasma cells are particularly addicted to SETD8 activity. Indeed, pharmacological inhibition of this enzyme by the chemical compound UNC0379 demonstrated a significantly higher toxicity in MM cells compared to normal cells from the bone marrow microenvironment. Moreover, RNA sequencing and functional studies revealed that SETD8 inhibition induces a mature non-proliferating plasma cell signature and an activation of the p53 canonical pathway, which together leads to an impairment of myeloma cell proliferation and survival. However, UNC0379 treatment triggers a deadly level of replicative stress in p53 deficient MM cells, indicating that the cytotoxicity associated with SETD8 inhibition is independent of the p53 status. Consistent with this, the combination of UNC0379 with the conventional cytotoxic agent melphalan strongly enhances DNA damage and overcomes drug resistance in myeloma cells. Thus, targeting SETD8 could be of therapeutic interest to improve MM treatment in high-risk patients independently of the p53 status.

cancer biology↗

bioRxiv2019

Mining the human tonsillar microbiota as autoimmune modulator

Palatine tonsils are important lymphoid organs featuring constant cross-talks between the commensal microorganisms and immune system, and have been implicated as critical autoimmunity origins for immune-related diseases, including rheumatoid arthritis (RA), a common autoimmune disorder. However, there was no evidence to show link between tonsillar microbiota and RA. Here, we identified a significant dysbiosis of RA tonsillar microbiota, with loss of Streptococcus salivarius and its functional molecules salivaricins (a type of antibacterial peptides). Consistent with the niche-preference, S. salivarius and salivaricins administrated intranasally or intraorally conferred prophylactic and therapeutic efficacies against experimental arthritis. Moreover, we demonstrated, for the first time, that S. salivarius and salivaricins exerted immunosuppressive capacities via inhibiting CD4+effector T cell subsets and autoantibody production in mice and human. These results uncover a communication between tonsillar microbiota and host autoimmunity, and identify the active components from tonsillar microbes in modulating immune homeostasis.\n\nOne sentence summaryTonsillar microbiota regulate host autoimmunity via antibacterial peptides

microbiology↗