A5052449076- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Pancreatic function and diabetes
- Autophagy in Disease and Therapy
- Autoimmune and Inflammatory Disorders Research
- Immunotherapy and Immune Responses
- Adipokines, Inflammation, and Metabolic Diseases
- interferon and immune responses
- Immune responses and vaccinations
- Calcium signaling and nucleotide metabolism
- Inflammasome and immune disorders
- Adenosine and Purinergic Signaling
- Cell death mechanisms and regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immunodeficiency and Autoimmune Disorders
- Psoriasis: Treatment and Pathogenesis
University of Science and Technology of China
2017-2024
Hefei National Center for Physical Sciences at Nanoscale
2024
Chinese Academy of Sciences
2023
Center for Excellence in Molecular Cell Science
2017
Abstract Dysfunction of invariant natural killer T (iNKT) cells in tumor microenvironment hinders their anti-tumor efficacy, and the underlying mechanisms remain unclear. Here we report that iNKT increase lipid biosynthesis after activation, is promoted by PPARγ PLZF synergically through enhancing transcription Srebf1 . Among those lipids, cholesterol required for optimal IFN-γ production from cells. Lactic acid reduces expression intratumoral consequently diminishes synthesis production....
Abstract Dysfunction of invariant natural killer T (iNKT) cells contributes to immune resistance tumors. Most mechanistic studies focus on their static functional status before or after activation, not considering motility as an important characteristic for antigen scanning and thus anti-tumor capability. Here we show via intravital imaging, that impaired iNKT exclusion from tumors both contribute the diminished cell response. Mechanistically, CD1d, expressed macrophages, interferes with...
Background and Aims: The innate-like mucosa-associated invariant T (MAIT) cells are enriched in human liver have been linked to HCC. However, their contributions the progression of HCC controversial due heterogeneity MAIT cells, new cell subsets remain be explored. Approach Results: Combining single RNA sequencing (scRNA-seq) flow cytometry analysis, we performed phenotypic functional studies found that FOXP3 + CXCR3 patients were regulatory (MAITregs) with high immunosuppressive potential....
Invariant natural killer T (iNKT) cells are innate-like lymphocytes that express an invariant cell receptor (TCR), which recognizes glycolipid antigens presented on CD1d molecules. These phenotypically and functionally distinct from conventional cells. When we characterized the metabolic activity of iNKT cells, consistent with their activated phenotype, found they had much less mitochondrial respiratory capacity but increased glycolytic in comparison to naïve CD4+ After TCR engagement,...
Murine caspase-11 is the centerpiece of non-canonical inflammasome pathway that can respond to intracellular LPS and induce pyroptosis. Caspase-11 contains two components, an N-terminal caspase recruitment domain (CARD) a C-terminal catalytic domain. The aggregation thought promote auto-processing activation caspase-11. However, mechanism remains unclear. In this study, we purified CARD fused MBP tag found it tetramerizes in solution. Crystallographic analysis reveals extensive hydrophobic...
Activation of mTORC1 is essential for anti-tumor function iNKT cells. The mechanisms underlying impaired activation in intratumoral cells remain unclear. Via generating Vam6 +/- mice and using flow cytometry, image approach, RNA sequencing, we studied the role controlling cell functions. Here, find that increased expression leads to IFN-γ production. Mechanistically, Rab7a-Vam6-AMPK complex formation thus recruitment AMPK lysosome activate AMPK, a negative regulator mTORC1. Additionally,...
CD8+ invariant natural killer T (iNKT) cells are functionally different from other iNKT and enriched in human but not mouse. To date, their developmental pathway molecular basis for fate decision remain unclear. Here, we report enrichment of neonatal mice due to more rapid maturation kinetics than CD8- cells. Along trajectories, separate at stage 0, following 0 double-positive cells, differ HIVEP3 expression. is lowly expressed negatively controls development, whereas it highly positively...
Background To investigate the phenotype and function of mucosal-associated invariant T (MAIT) cells in peripheral blood patients with Henoch-Schönlein purpura (HSP), owing to lack evidence on role MAIT HSP. Methods Blood samples from HSP healthy donors (HDs) were assessed by flow cytometry single-cell RNA sequencing (scRNA-seq) analyze proportion, phenotype, cells. We analyzed Th-cytokines serum cytometric bead array (CBA). IgA cocultured supernatant was detected CBA antibody production B...
Dysfunction of intratumoral invariant natural killer T (iNKT) cells hinders their antitumor efficacy, but the underlying mechanisms and relationship with endogenous antigen priming remain to be explored. Here, we report that leads metabolic reprogramming epigenetic remodeling, which causes functional in iNKT cells, characterized by limited cytokine responses upon restimulation constitutive high cytotoxicity. Mechanistically, impaired oxidative phosphorylation (OXPHOS) antigen-primed...
Background: Mucosal-associated invariant T (MAIT) cells are nonconventional with protection from infection. Sepsis is caused by severe life-threatening infection organ dysfunction; however, the relationships between host immune responses and disease severity not fully understood. Here, we explore phenotype, function clinical implications of MAIT in sepsis immunopathogenesis. Methods: Blood samples were collected 35 patients 46 healthy donors. The phenotypic functional properties analyzed...
<p>Antigen priming leads to dysfunction in distinct iNKT subsets.</p>
<p>A, Procedure for TCR signaling priming of human iNKT cells in vitro. B, The TMRM/MitoTracker ratio (n = 4) control and signaling-primed cells, the presence ZLN005 or DMSO as control. C, Frequencies IFN+ GzmB+ after restimulation with anti-CD3 plus anti-CD28 antibodies indicated (A) 7). Data are represented mean ± SD. Student’s t test was used to determine statistical significance (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, n.s., not significant).</p>
<div>Abstract<p>Dysfunction of intratumoral invariant natural killer T (iNKT) cells hinders their antitumor efficacy, but the underlying mechanisms and relationship with endogenous antigen priming remain to be explored. Here, we report that leads metabolic reprogramming epigenetic remodeling, which causes functional in iNKT cells, characterized by limited cytokine responses upon restimulation constitutive high cytotoxicity. Mechanistically, impaired oxidative phosphorylation...
<p>Supplementary Figure Legends</p>
<p>Gating strategy for identifying different lymphocytes in tumors.</p>
<p>Antigen priming leads to dysfunction in distinct iNKT subsets.</p>
<p>Supplementary Figure Legends</p>
<div>Abstract<p>Dysfunction of intratumoral invariant natural killer T (iNKT) cells hinders their antitumor efficacy, but the underlying mechanisms and relationship with endogenous antigen priming remain to be explored. Here, we report that leads metabolic reprogramming epigenetic remodeling, which causes functional in iNKT cells, characterized by limited cytokine responses upon restimulation constitutive high cytotoxicity. Mechanistically, impaired oxidative phosphorylation...
<p>A, Procedure for TCR priming in vitro. B-C, Frequencies of IFN+ (B), GzmA+, and GzmB+ (C) naïve TCR-primed iNKT cells restimulated with anti-CD3 plus anti-CD28 antibodies as indicated (A) (n = 3). Data are represented mean ± SD. Student’s t test was used to determine statistical significance (*P<0.05, ***P<0.001, n.s., not significant).</p>
<p>A, Procedure for TCR signaling priming of human iNKT cells in vitro. B, The TMRM/MitoTracker ratio (n = 4) control and signaling-primed cells, the presence ZLN005 or DMSO as control. C, Frequencies IFN+ GzmB+ after restimulation with anti-CD3 plus anti-CD28 antibodies indicated (A) 7). Data are represented mean ± SD. Student’s t test was used to determine statistical significance (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, n.s., not significant).</p>
<p>Gating strategy for identifying different lymphocytes in tumors.</p>
<p>A, Procedure for TCR priming in vitro. B-C, Frequencies of IFN+ (B), GzmA+, and GzmB+ (C) naïve TCR-primed iNKT cells restimulated with anti-CD3 plus anti-CD28 antibodies as indicated (A) (n = 3). Data are represented mean ± SD. Student’s t test was used to determine statistical significance (*P<0.05, ***P<0.001, n.s., not significant).</p>
Abstract Activation of mTORC1 is essential for anti-tumor function iNKT cells. The mechanisms underlying impaired activation in intratumoral cells remain unclear. Here, we showed that lactic acid from tumor increased Vam6 expression which led to and IFN-γ production. Mechanistically, was Rab7a-Vam6-AMPK complex formation thus recruitment AMPK lysosome activate AMPK, a negative regulator mTORC1. Additionally, relieved inhibitory effect VDAC1 on at mitochondria-lysosome contact site. Given the...