Glutaminolysis promotes the function of follicular helper T cells in lupus-prone mice DOI Open Access

Seung Chul Choi,

Yong Ge, Mohit Joshi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Abstract Glutamine metabolism is essential for T cell activation and functions. The inhibition of glutaminolysis impairs Th17 differentiation alters Th1 There evidence an active in the immune cells lupus patients. Treatment lupus-prone mice with inhibitors ameliorated disease association a reduced frequency cells. This study was performed to determine role murine Tfh cells, critical subset helper CD4 + that provide help autoreactive B produce autoantibodies. We showed present high level glutamine metabolism. pharmacological DON had little effect on healthy mice, but it expression costimulatory molecule ICOS reduction autoantibody production, germinal center dynamics, as well atypical age-related plasma Accordingly, profound transcriptomic metabolic changes, including glycolysis, were induced by DON, while changes. cell-specific deletion gene encoding glutaminase enzyme GLS1 largely phenocopied effects autoimmune genetic background congenic control background. These results confirmed model lupus. Finally, we Gls1 impaired T- dependent humoral responses their response viral infection. Overall, these demonstrated greater intrinsic requirement functions, they suggest targeting may be beneficial treat

Language: Английский

The implications of FASN in immune cell biology and related diseases DOI Creative Commons
Y Xiao, Yonghong Yang, Huabao Xiong

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 25, 2024

Abstract Fatty acid metabolism, particularly fatty synthesis, is a very important cellular physiological process in which nutrients are used for energy storage and biofilm synthesis. As key enzyme the synthase (FASN) receiving increasing attention. Although previous studies on FASN have mainly focused various malignancies, many recently reported that regulates survival, differentiation, function of immune cells, subsequently participates occurrence development immune-related diseases. However, few to date systematically summarized molecular mechanisms cell biology related In this review, we discuss regulatory effect progress research implications Understanding diseases can offer insights into novel treatment strategies clinical

Language: Английский

Citations

24
Lysosomal endonuclease RNase T2 and PLD exonucleases cooperatively generate RNA ligands for TLR7 activation DOI Creative Commons
Marleen Bérouti, Katja Lammens, Matthias Heiß

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(7), P. 1482 - 1496.e8

Published: May 1, 2024

Toll-like receptor 7 (TLR7) is essential for recognition of RNA viruses and initiation antiviral immunity. TLR7 contains two ligand-binding pockets that recognize different degradation products: pocket 1 recognizes guanosine, while 2 coordinates pyrimidine-rich fragments. We found the endonuclease RNase T2, along with 5′ exonucleases PLD3 PLD4, collaboratively generate ligands TLR7. Specifically, T2 generated guanosine 2′,3′-cyclic monophosphate-terminated PLD exonuclease activity further released terminal monophosphate (2',3'-cGMP) to engage was also needed fragments 2. Loss-of-function studies in cell lines primary cells confirmed critical requirement activity. Biochemical structural showed enzymes form homodimers sites important Previously identified disease-associated mutants failed stable dimers. Together, our data provide a mechanistic basis detection by

Language: Английский

Citations

18
SARS-CoV-2 immunity in animal models DOI Creative Commons
Chen Zhao,

Yaochang Yuan,

Qing‐Tao Hu

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(2), P. 119 - 133

Published: Jan. 18, 2024

The COVID-19 pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide health crisis due to its transmissibility. SARS-CoV-2 infection results in illness and can lead significant complications affected individuals. These encompass symptoms such as coughing, distress, fever, infectious shock, distress (ARDS), even multiple-organ failure. Animal models serve crucial tools for investigating pathogenic mechanisms, immune responses, escape antiviral drug development, vaccines against SARS-CoV-2. Currently, various animal infection, nonhuman primates (NHPs), ferrets, hamsters, many different mouse models, have been developed. Each model possesses distinctive features applications. In this review, we elucidate the response elicited patients provide an overview of characteristics mainly used well corresponding responses applications these models. A comparative analysis transcriptomic alterations lungs from revealed that K18-hACE2 mouse-adapted virus exhibited highest similarity with deceased patients. Finally, highlighted current gaps related research between studies clinical investigations, underscoring lingering scientific questions demand further clarification.

Language: Английский

Citations

17
The TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse DOI Creative Commons
Ales Drobek, Léa Bernaleau, Maeva Delacrétaz

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 24, 2025

Abstract Endosomal nucleic acid sensing by Toll-like receptors (TLRs) is central to antimicrobial immunity and several autoimmune conditions such as systemic lupus erythematosus (SLE). The innate immune adaptor TASL mediates, via the interaction with SLC15A4, activation of IRF5 downstream human TLR7, TLR8 TLR9, but pathophysiological functions this axis remain unexplored. Here we show that SLC15A4 deficiency results in a selective block TLR7/9-induced activation, while loss leads strong incomplete impairment, which depends on cell type TLR engaged. This residual activity ascribed previously uncharacterized paralogue, Gm6377 , named here TASL2. Double knockout TASL2 (TASL DKO ) phenocopies SLC15A4-deficient feeble mice showing comparable impairment humoral responses. Consequently, fail control chronic LCMV infection, being protected pristane-induced SLE disease model. Our study thus demonstrates critical role TASL/TASL2 for TLR7/9-driven inflammatory responses, further supporting therapeutic potential targeting complex related diseases.

Language: Английский

Citations

2
Spatiotemporal release of non-nucleotide STING agonist and AKT inhibitor from implantable 3D-printed scaffold for amplified cancer immunotherapy DOI
Haixia Wang, Zheng Liu,

Youqiang Fang

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122645 - 122645

Published: May 28, 2024

Language: Английский

Citations

11
Immunoregulatory programs in anti‐N‐methyl‐D‐aspartate receptor encephalitis identified by single‐cell multi‐omics analysis DOI Creative Commons
Xinhui Li,

Yicong Xu,

Weixing Zhang

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Background Anti‐ N ‐methyl‐D‐aspartate receptor encephalitis (anti‐NMDARE) is a prevalent type of autoimmune caused by antibodies targeting the NMDAR's GluN1 subunit. While significant progress has been made in elucidating pathophysiology diseases, immunological mechanisms underlying anti‐NMDARE remain elusive. This study aimed to characterize immune cell interactions and dysregulation leveraging single‐cell multi‐omics sequencing technologies. Methods Peripheral blood mononuclear cells (PBMCs) from patients acute phase healthy controls were sequenced using joint profiling transcriptome chromatin accessibility. Differential gene expression analysis, transcription factor activity profiling, cell‐cell communication modeling performed elucidate disease. In parallel, B (scBCR‐seq) repertoire analysis conducted assess antigen‐driven clonal expansion within population. Results The revealed cells, particularly plasma patients. novel finding I interferon (IFN‐I) pathway activation suggests regulatory mechanism that may drive this enhance antibody secretion. Additionally, Toll‐like 2 (TLR2) myeloid was noted, which connect tumor necrosis factor‐alpha (TNF‐α) cytokine contribute T thereby perpetuating dysregulation. Conclusions presents comprehensive characterization anti‐NMDARE, highlighting IFN‐I TLR2 pathways. These findings provide deeper insights into molecular driving pathogenesis offer promising targets for future therapeutic intervention. Key points Significant expansion, driven antigen recognition. boosts their production potentially exacerbates contributes TNF‐α secretion could influence adaptive responses.

Language: Английский

Citations

1
Engineering mesoporous polydopamine-based potentiate STING pathway activation for advanced anti-biofilm therapy DOI
Shicheng Huo, Zhuocheng Lyu, Xiaoyuan Wang

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 312, P. 122739 - 122739

Published: July 31, 2024

Language: Английский

Citations

5
Mapping Human Immunity and the Education of Waldeyer's Ring DOI
Benjamin James Talks, Michael Mather,

Manisha Chahal

et al.

Annual Review of Genomics and Human Genetics, Journal Year: 2024, Volume and Issue: 25(1), P. 161 - 182

Published: April 10, 2024

The development and deployment of single-cell genomic technologies have driven a resolution revolution in our understanding the immune system, providing unprecedented insight into diversity cells present throughout body their function health disease. Waldeyer's ring is collective name for lymphoid tissue aggregations upper aerodigestive tract, comprising palatine, pharyngeal (adenoids), lingual, tubal tonsils. These tonsils are first sentinels encountered by ingested inhaled antigens responsible mounting wave adaptive response. An effective mucosal response critical to neutralizing infection airway preventing systemic spread, dysfunctional responses can result ear, nose, throat pathologies. This review uses demonstrate how being applied advance system highlight directions future research.

Language: Английский

Citations

4
Nanoparticle targeting cGAS-STING signaling in disease therapy DOI
Zhou Lan,

Yu Huang,

Yuzhang Wu

et al.

Nano Research, Journal Year: 2024, Volume and Issue: 17(8), P. 7315 - 7336

Published: June 15, 2024

Language: Английский

Citations

4
Innate Immune Receptors as Dynamic Modulators of Extrafollicular Autoimmune B Cell Response DOI Open Access
Yi Dan Zhu, Carlos Castrillón, Michael C. Carroll

et al.

Immunological Reviews, Journal Year: 2025, Volume and Issue: 330(1)

Published: Feb. 7, 2025

The immune system relies on carefully calibrated cellular machineries to enable distinction between endogenous and foreign molecules, with autoimmunity arising when this balance is disrupted. As potent autoantibody factories, B cells are major drivers of many autoimmune diseases. A significant fraction patients affected by chronic diseases such as systemic lupus erythematosus (SLE) exhibit pathogenic accumulation B-cell subsets that believed be derived from the extrafollicular (EF) differentiation pathway. These subsets, although variously named exhibiting intrinsic heterogeneity, all poised producers autoantibodies correlate patient pathophysiology. In addition, they often characterized biomarkers known drive innate response, including toll-like receptors complement receptors. Although have well-established functions in myeloid other cell types, their cell-specific still under active investigation crucial for understanding molecular pathways breaks tolerance. review, we summarize studies serve prominent roles regulating EF activation health autoimmunity. By discussing independent collaborative these receptors, hope provide new perspectives disease signature research.

Language: Английский

Citations

0