XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(6), P. 1043 - 1054

Published: May 20, 2021

Language: Английский

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Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes

Nature, Journal Year: 2023, Volume and Issue: 623(7987), P. 616 - 624

Published: Nov. 8, 2023

Abstract Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction 1 . There currently no cure for rheumatoid arthritis, the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity 1,2 Here, to deconstruct cell states pathways characterize this heterogeneity, we profiled full spectrum cells in inflamed synovium from patients with arthritis. We used multi-modal single-cell RNA-sequencing surface protein data coupled histology synovial tissue 79 donors build atlas includes more than 314,000 cells. stratified tissues into six groups, referred as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched states. These CTAPs demonstrate ranging samples T B those largely lacking lymphocytes. Disease-relevant states, cytokines, risk genes, serology metrics are associated particular CTAPs. dynamic can predict treatment response, highlighting clinical utility classifying phenotypes. This comprehensive molecular, tissue-based stratification reveal new insights pathology heterogeneity could inform novel targeted treatments.

Language: Английский

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Microbiota‐Driven Activation of Intrahepatic B Cells Aggravates NASH Through Innate and Adaptive Signaling

Hepatology, Journal Year: 2021, Volume and Issue: 74(2), P. 704 - 722

Published: Feb. 20, 2021

Background and Aims Nonalcoholic steatohepatitis is rapidly becoming the leading cause of liver failure indication for transplantation. Hepatic inflammation a key feature NASH but immune pathways involved in this process are poorly understood. B lymphocytes cells adaptive system that critical regulators responses. However, role pathogenesis potential mechanisms to their activation unclear. Approach Results In study, we report livers accumulate with elevated pro‐inflammatory cytokine secretion antigen‐presentation ability. Single‐cell bulk RNA sequencing intrahepatic from mice unveiled transcriptional landscape reflects function. Accordingly, B‐cell deficiency ameliorated progression, adoptively transferring recapitulates disease. Mechanistically, during involves signaling through innate adaptor myeloid differentiation primary response protein 88 (MyD88) as cell–specific deletion MyD88 reduced hepatic T cell–mediated fibrosis, not steatosis. addition, implicates cell–receptor signaling, delineating synergy between antigen recognition. Furthermore, fecal microbiota transplantation human NAFLD gut microbiotas into recipient promoted progression by increasing accumulation cells, suggesting microbial factors drive pathogenic function NASH. Conclusion Our findings reveal microbiota–driven leads fibrosis mechanisms.

Language: Английский

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Monocytes, macrophages, dendritic cells and neutrophils: an update on lifespan kinetics in health and disease

Immunology, Journal Year: 2021, Volume and Issue: 163(3), P. 250 - 261

Published: Feb. 8, 2021

Summary Phagocytes form a family of immune cells that play crucial role in tissue maintenance and help orchestrate the response. This can be separated by their nuclear morphology into mononuclear polymorphonuclear phagocytes. The generation these bone marrow, to blood finally tissues is tightly regulated process. Ensuring adequate production timely removal key for both initiation resolution inflammation. Insight kinetic profiles innate myeloid during steady state pathology will permit rational development therapies boost times need or reduce them when detrimental.

Language: Английский

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Roles of macrophages in tumor development: a spatiotemporal perspective

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(9), P. 983 - 992

Published: July 10, 2023

Abstract Macrophages are critical regulators of tissue homeostasis but also abundant in the tumor microenvironment (TME). In both primary tumors and metastases, such tumor-associated macrophages (TAMs) seem to support development. While we know that TAMs dominant immune cells TME, their vast heterogeneity associated functions only just being unraveled. this review, outline various known TAM populations found thus far delineate specialized roles with main stages cancer progression. We discuss how may prime premetastatic niche enable growth a metastasis then subsequent metastasis-associated can secondary growth. Finally, speculate on challenges remain be overcome research.

Language: Английский

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