A5102776741- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- T-cell and B-cell Immunology
- Cancer-related molecular mechanisms research
- Liver Disease Diagnosis and Treatment
- Diabetes and associated disorders
- Mycobacterium research and diagnosis
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Circular RNAs in diseases
- Immune cells in cancer
- RNA modifications and cancer
- Drug Solubulity and Delivery Systems
- Alcohol Consumption and Health Effects
- MicroRNA in disease regulation
- Advanced Drug Delivery Systems
- Cytokine Signaling Pathways and Interactions
- Diet, Metabolism, and Disease
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Blood Coagulation and Thrombosis Mechanisms
- Cancer, Hypoxia, and Metabolism
- Protein Tyrosine Phosphatases
- Cardiac Ischemia and Reperfusion
Heilongjiang University of Chinese Medicine
2024-2025
West China Hospital of Sichuan University
2025
Central South University
2025
Sichuan University
2025
Hebei Medical University
2024
Huazhong University of Science and Technology
2010-2024
First Affiliated Hospital of Anhui Medical University
2024
Anhui Medical University
2024
Rockefeller University
2019-2024
Harbin Medical University
2019-2024
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 987 patients with life-threatening disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), 13 types IFN-α (36), or both (52) onset critical disease; a few also auto-Abs other three type I IFNs. The neutralize ability corresponding IFNs to block...
The genetics underlying severe COVID-19 immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody dampens IFN response prevent damage from pathogen-induced inflammation. Two studies now examine likelihood affects risk of coronavirus disease 2019 (COVID-19) through components this (see Perspective by Beck Aksentijevich). Q....
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found about 10% patients with critical COVID-19 pneumonia, but not subjects asymptomatic infections. We detect auto-Abs 100-fold lower, more physiological, (100 pg/mL, 1/10 dilutions plasma) 13.6% 3,595 COVID-19, including 21% 374 > 80 years, and 6.5% 522 severe COVID-19. These antibodies also detected 18% the 1,124 deceased (aged 20 days-99 years; mean: 70...
Abstract Background Increasing studies have shown that circRNA is closely related to the carcinogenesis and development of many cancers. However, biological functions underlying molecular mechanism circRNAs in triple-negative breast cancer (TNBC) remain largely unclear so far. Methods Here, we investigated expression pattern four pairs TNBC tissues paracancerous normal using RNA-sequencing. The prognostic significance circSEPT9 were evaluated with qRT-PCR situ hybridization two cohorts....
Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported one 12-yr-old patient. Here, we studied seven other previously healthy aged 13 to 80 yr unexplained YFV vaccine–associated disease. One 13-yr-old patient had AR IFNAR2 deficiency. Three vaccinated at the ages 47, 57, and 64 high titers circulating auto-Abs...
Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It important to estimate their quantitative impact on mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence these risk death increase with higher in men. Using an unvaccinated sample 1,261 deceased patients 34,159 individuals from general population, we found against IFNs strongly increased...
Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn IFN-α/β-dependent intrinsic viral diseases. Both types IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria related intramacrophagic pathogens. These have no history severe disease, despite exposure to many viruses, including...
Patients with autosomal recessive (AR) IL-12p40 or IL-12Rβ1 deficiency display Mendelian susceptibility to mycobacterial disease (MSMD) due impaired IFN-γ production and, less commonly, chronic mucocutaneous candidiasis (CMC) IL-17A/F production. We report six patients from four kindreds AR IL-23R deficiency. These are homozygous for one of different loss-of-function IL23R variants. All have a history MSMD, but only two suffered CMC. show that IL-23 induces IL-17A in MAIT cells, possibly...
IL-6 is known to contribute the differentiation of CD4+ T cells into different subsets effector helper cells. Less about potential in regulating CD8+ cell function. Here, we identify as a master regulator IL-21 promotes subset naive that express IL-6R unique population characterized by production high levels and low IFN-γ. Similar follicular (Tfh) cells, IL-21–producing generated presence directly provide help B induce isotype switching. cell–derived contributes protective virus-specific IgG...
Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by a selective predisposition clinical caused the Bacille Calmette-Guérin (BCG) vaccine and environmental mycobacteria. The known genetic etiologies of MSMD are inborn errors IFN-γ immunity due mutations 15 genes controlling production or response IFN-γ. Since first MSMD-causing were reported in 1996, biallelic encoding receptor 1 (IFN-γR1) IFN-γR2 have been many patients diverse ancestries. Surprisingly, gene cytokine...
Significance Only ∼5% of individuals infected with Mycobacterium tuberculosis develop clinical TB in their lifetime. We previously reported that homozygosity for the P1104A variant TYK2 gene, found ∼1/600 Europeans and ∼1/5,000 from elsewhere (except East Asians sub-Saharan Africans), was a monogenic etiology genetically heterogeneous cohort patients non-European countries endemic TB. Making use UK Biobank cohort, we report strong enrichment homozygotes British sample 620 (1%), relative to...
Protein kinase B (PKB/Akt) plays important roles in the regulation of lipid homeostasis, and impairment Akt activity has been demonstrated to be involved development non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that cytochrome P4502E1 (CYP2E1) causal pathogenesis alcoholic (AFL). We hypothesized might impaired due CYP2E1-induced oxidative stress chronic ethanol-induced hepatic steatosis. In this study, we found steatosis was accompanied with reduced phosphorylation at...
Human inborn errors of IFN-γ underlie mycobacterial disease, due to insufficient production by lymphoid cells, impaired myeloid cell responses this cytokine, or both. We report four patients from two unrelated kindreds with intermittent monocytosis and including bacillus Calmette-Guérin-osis disseminated tuberculosis, without any known error IFN-γ. The are homozygous for ZNFX1 variants (p.S959* p.E1606Rfs*10) predicted be loss function (pLOF). There no subjects pLOF in public databases. is a...
High-level expression of the transcription factor T-bet characterizes a phenotypically distinct murine B cell population known as “age-associated cells” (ABCs). T-bet–deficient mice have reduced ABCs and impaired humoral immunity. We describe patient with inherited deficiency largely normal immunity including intact somatic hypermutation, affinity maturation memory formation in vivo, differentiation into Ig-producing plasmablasts vitro. Nevertheless, exhibited skewed class switching to IgG1,...
The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes life-threatening necrosis, typically triggered S. infection. disorder phenocopied in 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN causes an accumulation ubiquitin dermal fibroblasts, but tumor necrosis factor receptor-mediated...
Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and IL-12 IL-23 mycobacterial diseases). Cells common P1104A allele selectively impaired isolated disease). We report three new forms of deficiency six patients from five families (R864C, G996R, G634E, or G1010D) compound heterozygous a (A928V). All these missense encode detectable proteins. The R864C G1010D are...
Ventilator-induced lung injury (VILI) is caused by overdistension of the alveoli repetitive recruitment and derecruitment alveolar units. This study aims to investigate potential role mechanism fibroblast growth factor 21 (FGF21), a metabolic regulator secreted liver, in VILI development.Serum FGF21 concentrations were determined patients undergoing mechanical ventilation during general anesthesia mouse model. Lung was compared between FGF21-knockout (KO) mice wild-type (WT) mice....
Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder only tuberculosis