A5024699628- interferon and immune responses
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Asthma and respiratory diseases
- T-cell and B-cell Immunology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- RNA regulation and disease
- Viral Infections and Vectors
- Urticaria and Related Conditions
- IgG4-Related and Inflammatory Diseases
- vaccines and immunoinformatics approaches
- BRCA gene mutations in cancer
- Eosinophilic Disorders and Syndromes
- Pneumonia and Respiratory Infections
- Transplantation: Methods and Outcomes
- Pediatric health and respiratory diseases
- Alkaline Phosphatase Research Studies
- Sarcoidosis and Beryllium Toxicity Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Polyomavirus and related diseases
- Hedgehog Signaling Pathway Studies
- Sulfur Compounds in Biology
University of Florida
2016-2022
Tabaran Institute of Higher Education
2021
Florida College
2020
Albany Medical Center Hospital
2015-2018
University of Tehran
2013
Genethon (France)
2007
Université Paris-Est Créteil
2002
Hôpital Rothschild
1997
Sorbonne Université
1997
Effective mucosal adjuvants enhance the magnitude and quality of vaccine response. Cyclic di-GMP (CDG) is a promising adjuvant. However, its in vivo mechanisms are unclear. Here, we showed, mice, that CDG elicits stronger Ab TH responses than mammalian 2'3'-cyclic GMP-AMP (cGAMP), generated better protection against Streptococcus pneumoniae infection 2'3'-cGAMP adjuvanted vaccine. We identified two CDG. First, intranasally administered greatly enhances Ag uptake, including pinocytosis...
Abstract Polyubiquitination promotes proteasomal degradation, or signaling and localization, of targeted proteins. Here we show that the E3 ubiquitin ligase Hectd3 is necessary for pathogenic Th17 cell generation in experimental autoimmune encephalomyelitis (EAE), a mouse model human multiple sclerosis. Hectd3-deficient mice have lower EAE severity, reduced program inefficient differentiation. However, Stat3, but not RORγt, has decreased polyubiquitination, as well diminished tyrosine-705...
Abstract TMEM173 encodes MPYS/STING and is an innate immune sensor for cyclic dinucleotides (CDNs) playing a critical role in infection, inflammation, cancer. The R71H-G230A-R293Q (HAQ) of the second most common human allele. In this study, using data from 1000 Genomes Project we found that homozygous HAQ individuals account ∼16.1% East Asians ∼2.8% Europeans whereas Africans have no individuals. Using B cells carriers, found, surprisingly, HAQ/HAQ carriers express extremely low MPYS protein...
The lung is a naturally tolerogenic organ. Lung regulatory T cells (T-regs) control mucosal tolerance. Here, we identified IFNAR1hiTNFR2+ conventional DC2 (iR2D2) population that induces T-regs in the at steady state. Using conditional knockout mice, adoptive cell transfer, receptor blocking antibodies, and TNFR2 agonist, showed iR2D2 microenvironment-adapted dendritic whose residence depends on constitutive signaling. IFNβ-IFNAR1 signaling necessary sufficient for induction lung....
Although activation of adaptive immunity is a common pathological feature chronic obstructive pulmonary disease (COPD), particularly during later stages the disease, underlying mechanisms are poorly understood. In small airways COPD patients, we found that localized disruption secretory immunoglobulin A (SIgA)-containing mucosal immunobarrier correlated with lymphocyte accumulation in airway walls and development tertiary lymphoid structures (TLS) around airways. SIgA-deficient mice,...
Cyclic dinucleotides (CDNs), including cyclic di-GMP (CDG), are promising vaccine adjuvants in preclinical/clinical trials. The vivo mechanisms of CDNs not clear. Here we investigated the roles lung DC subsets promoting CDG mucosal adjuvant responses vivo. Using genetically modified mice and adoptive cell transfer, identified conventional 2 (cDC2) as central player responses. We further two functionally distinct cDC2 subpopulations: TNFR2+pRelB+ TNFR2−pRelB− cDC2. TNFR2+ were mature...
Abstract MPYS/STING (stimulator of IFN genes) senses cyclic dinucleotides (CDNs), generates type I IFNs, and plays a critical role in infection, inflammation, cancer. In this study, analyzing genotype haplotype data from the 1000 Genomes Project, we found that R71H-G230A-R293Q (HAQ) MPYS allele frequency increased 57-fold East Asians compared with sub-Saharan Africans. Meanwhile, G230A-R293Q (AQ) decreased by 98% We propose HAQ AQ alleles underwent natural selection during out-of-Africa...
Asthma is a common inflammatory lung disease with no known cure. Previously, we uncovered TNFR2+ conventional DC2 subset (cDC2s) that induces regulatory T cells (Tregs) maintaining tolerance at steady state but promotes TH2 response during house dust mite (HDM)-induced asthma. Lung IFNβ essential for cDC2s-mediated tolerance. Here, showed exogenous reprogrammed TH2-promoting pathogenic cDC2s back to tolerogenic DCs, alleviating eosinophilic asthma and preventing exacerbation....
Induction of lung mucosal immune responses is highly desirable for vaccines against respiratory infections. We recently showed that monocyte-derived dendritic cells (moDCs) are responsible IgA induction. However, the cell subset inducing memory TH unknown. In this study, using conditional knockout mice and adoptive transfer, we found moDCs essential but dispensable systemic vaccine responses. Next, adjuvant cyclic di-GMP differentiated into Bcl6+ mature promoting cells, they production....
The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) pathway senses DNA and induces type I (IFN) production. Whether how the STING crosstalk to other innate immune pathways during pathogen infection, however, remains unclear. Here, we showed that was needed for Streptococcus pneumoniae -induced late, not early, stage lung IFNγ Using knockout mice, reporter intracellular cytokine staining, adoptive cell transfer, cGAS–STING-dependent production independent IFNs....
Cyclic dinucleotides (CDNs) are promising vaccine adjuvants inducing balanced, potent humoral, and cellular immune responses. How aging influences CDN efficacy is unclear. We examined the of 3',5'-cyclic diguanylic acid (cyclic di-GMP, CDG), founding member CDNs, in 1-year-old (middle-aged) 2-year-old (aged) C57BL/6J mice. found that 1- mice defective CDG-induced memory T helper (Th)1 Th17 responses high-affinity serum immunoglobulin (Ig)G, mucosal IgA production. Next, we generated two...
Credit risk is one of important challenges facing banks and credit institutions in all economic systems.Accordingly, much research has focused on scoring bank customers to predict classify solventcustomers insolvent customers. In this line, the present study attempted identify employ financialratios affecting creditworthiness banking using discriminant analysis logistic regression todetermine reliability different models predicting customers.To do so, customers’ files branches commercial...
The efficacy of acceptance and commitment therapy comparing it with cognitive behavioral on coping methods, difficulty in emotion regulation, mental health among caretakers chronic patients
Intranasal administration of vaccine adjuvants directly deliver therapeutic agents to the lungs induce potent lung mucosal immune responses. Cyclic di-GMP (CDG) is a promising adjuvant candidate capable inducing protective immunity. This protocol describes an in vivo approach and detect (lung) systemic (blood spleen) responses CDG. also includes methods both humoral cellular CDG adjuvant. Last, this can be used study other cyclic dinucleotides as adjuvants.
Abstract Induction of lung T-cell responses, including memory CD4 + T H and FH cells, are highly desirable for vaccines against respiratory infections. We recently showed that the non-migratory monocytes-derived DCs (moDCs) induced cells. However, subset inducing cells is unknown. Here, using conditional knockout mice adoptive cell transfer, we first established moDCs essential mucosal, but dispensable systemic, vaccine responses. Next, intranasal administration adjuvant cyclic di-GMP...
Abstract The mucosal surface is the major entry site for many human pathogens, however there are only a dozen of vaccines approved use. challenge to develop safe and effective adjuvants. 3′, 5′-Cyclic di-GMP (CDG) an attractive vaccine adjuvant candidate that activates STING (stimulator interferon genes). However, in vivo mechanism action CDG not completely understood. Our previous studies found intranasal immunization with directly pulmonary dendritic cells (DCs). We activity depends on...