Single-cell landscape of functionally cured chronic hepatitis B patients reveals activation of innate and altered CD4-CTL-driven adaptive immunity DOI Creative Commons

Balakrishnan Chakrapani Narmada,

Atefeh Khakpoor, Niranjan Shirgaonkar

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(1), P. 42 - 61

Published: Feb. 28, 2024

Background & AimsHepatitis B surface antigen (HBsAg) loss or functional cure (FC), is considered the desirable therapeutic outcome for chronic hepatitis (CHB) patients. However, immune-pathological biomarkers and underlying mechanisms remain unclear. In this study we comprehensively interrogate disease-associated cell states (DACS) identified within intra-hepatic tissue matched PBMCs from either CHB FC patients, at resolution of single cells, to provide novel insights into putative FC.MethodsWe combined transcriptomics (scRNA-seq) with multiparametric flow cytometry-based immune phenotyping, multiplexed immunofluorescence elucidate immunopathological associated vs FC.ResultsWe find that environment patients displays specific identities molecular signatures are distinct those found in PBMCs. emergence an altered adaptive response marked by CD4 cytotoxic T lymphocytes (CD4-CTLs), activated innate represented liver-resident natural killer (LR-NK) Kupffer (KC) subtypes marginated neutrophils. Surprisingly, also characterized presence MHC class II-expressing hepatocytes low but persistent levels cccDNA pgRNA, which may play important role achieving HBV patients.ConclusionsOur provides conceptually immuno-pathological control cure, opens exciting new avenues clinical management, biomarker discovery interventions. We believe discoveries study, as it relates activation facilitate sustained, low-grade inflammation, have broader implications viral hepatitis.

Language: Английский

Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas DOI
Reuben Moncada, Dalia Barkley, Florian Wagner

et al.

Nature Biotechnology, Journal Year: 2020, Volume and Issue: 38(3), P. 333 - 342

Published: Jan. 13, 2020

Language: Английский

Citations

779
Revisiting the role of CD4+ T cells in cancer immunotherapy—new insights into old paradigms DOI Creative Commons
Rong En Tay,

Emma K. Richardson,

Han Chong Toh

et al.

Cancer Gene Therapy, Journal Year: 2020, Volume and Issue: 28(1-2), P. 5 - 17

Published: May 26, 2020

Cancer immunotherapy has revolutionised cancer treatment, with immune checkpoint blockade (ICB) therapy and adoptive cell (ACT) increasingly becoming standard of care across a growing number indications. While the majority immunotherapies focus on harnessing anti-tumour CD8+ cytotoxic T response, potential role CD4+ 'helper' cells largely remained in background. In this review, we give an overview multifaceted emphasis recent evidence that play bigger than previously thought. We illustrate their direct potency directing sustained response against tumours. further highlight emerging observation responses tumours tend to be self-derived epitopes. These trends raise vital questions considerations will profoundly affect rational design leverage full system cancer.

Language: Английский

Citations

637
The Immune Functions of Keratinocytes in Skin Wound Healing DOI Open Access
Minna Piipponen, Dongqing Li, Ning Xu

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(22), P. 8790 - 8790

Published: Nov. 20, 2020

As the most dominant cell type in skin, keratinocytes play critical roles wound repair not only as structural cells but also exerting important immune functions. This review focuses on communications between and healing, which are mediated by various cytokines, chemokines, extracellular vesicles. Keratinocytes can directly interact with T via antigen presentation. Moreover, produce antimicrobial peptides that kill invading pathogens contribute to many aspects. We reviewed epigenetic mechanisms known regulate keratinocyte functions, including histone modifications, non-protein-coding RNAs (e.g., microRNAs, long noncoding RNAs), chromatin dynamics. Lastly, we summarized current evidence dysregulated functions of chronic nonhealing wounds. Based their crucial skin propose significantly pathogenesis inflammation. hope this will trigger an interest investigating pathology, may open up new avenues for developing innovative treatments.

Language: Английский

Citations

339
Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients DOI Open Access
Tianxiao Liu, Songyuan Luo, Peter Libby

et al.

Pharmacology & Therapeutics, Journal Year: 2020, Volume and Issue: 213, P. 107587 - 107587

Published: May 27, 2020

Language: Английский

Citations

278
Temporal Dynamics and Heterogeneity of Cell Populations during Skeletal Muscle Regeneration DOI Creative Commons

Stephanie N. Oprescu,

Feng Yue, Jiamin Qiu

et al.

iScience, Journal Year: 2020, Volume and Issue: 23(4), P. 100993 - 100993

Published: March 20, 2020

Mammalian skeletal muscle possesses a unique ability to regenerate, which is primarily mediated by population of resident stem cells (MuSCs) and requires concerted response from other supporting cell populations. Previous targeted analysis has described the involvement various specific populations in regeneration, but an unbiased simultaneous evaluation all been limited. Therefore, we used single-cell RNA-sequencing uncover gene expression signatures over 53,000 individual during regeneration. Cells clustered into 25 subpopulations, including subpopulation immune enriched myoblasts (immunomyoblasts) subpopulations fibro-adipogenic progenitors. Our analyses also uncovered striking spatiotemporal dynamics expression, composition, cell-cell interaction These findings provide insights cellular molecular underpinning

Language: Английский

Citations

210
Single-cell transcriptomic analysis defines the interplay between tumor cells, viral infection, and the microenvironment in nasopharyngeal carcinoma DOI Open Access
Shanzhao Jin, Ruoyan Li, Ming‐Yuan Chen

et al.

Cell Research, Journal Year: 2020, Volume and Issue: 30(11), P. 950 - 965

Published: Sept. 8, 2020

Language: Английский

Citations

168
arcasHLA: high-resolution HLA typing from RNAseq DOI Creative Commons
Rose Orenbuch,

Ioan Filip,

Devon Comito

et al.

Bioinformatics, Journal Year: 2019, Volume and Issue: 36(1), P. 33 - 40

Published: June 3, 2019

The human leukocyte antigen (HLA) locus plays a critical role in tissue compatibility and regulates the host response to many diseases, including cancers autoimmune di3orders. Recent improvements quality accessibility of next-generation sequencing have made HLA typing from standard short-read data practical. However, this task remains challenging given high level polymorphism homology between genes. RNA is further complicated by post-transcriptional modifications bias due amplification.Here, we present arcasHLA: fast accurate silico tool that infers genotypes RNA-sequencing data. Our outperforms established tools on gold-standard benchmark dataset for terms both accuracy speed, with an rate 100% at two-field resolution Class I genes, over 99.7% II. Furthermore, evaluate performance our new biological 447 single-end total samples nasopharyngeal swabs, establish applicability arcasHLA metatranscriptome studies.arcasHLA available https://github.com/RabadanLab/arcasHLA.Supplementary are Bioinformatics online.

Language: Английский

Citations

157
Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts DOI Creative Commons
Dimitra Kerdidani, Emmanouil Aerakis, Kleio‐Maria Verrou

et al.

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(2)

Published: Jan. 14, 2022

A key unknown of the functional space in tumor immunity is whether CD4 T cells depend on intratumoral MHCII cancer antigen recognition. MHCII-expressing, antigen-presenting cancer-associated fibroblasts (apCAFs) have been found breast and pancreatic tumors are considered to be immunosuppressive. This analysis shows that frequent human lung non-small cell carcinomas, where they seem actively promote rather than suppress immunity. Lung apCAFs directly activated TCRs effector at same time produced C1q, which acted C1qbp rescue them from apoptosis. Fibroblast-specific or C1q deletion impaired accelerated growth, while inducing adoptively transferred expanded their numbers reduced tumors. Collectively, we characterized lungs a subset with tumor-suppressive properties propose immunotherapies might strongly dependent situ presentation.

Language: Английский

Citations

123
The function of gut microbiota in immune-related neurological disorders: a review DOI Creative Commons
Panida Sittipo,

Jaeyoon Choi,

Soojin Lee

et al.

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: June 15, 2022

This review provides an overview of the importance microbiota in regulation gut-brain communication immune-related neurological disorders. The gastrointestinal (GI) tract hosts a diverse abundance microbiota, referred to as gut microbiota. plays role maintenance GI homeostasis and is likely have multiple effects on brain development function. bidirectional between termed microbiota-gut-brain axis. intestine appears affect human health behavior, certain animal studies demonstrated association alterations Most insights about axis come from germ-free models, which reveal neural To date, many observed impact patients with Although investigated axis, there are still limitations translating this research humans given complexities relationship brain. In review, we discuss emerging evidence how regulates function through biological networks, well possible contribution

Language: Английский

Citations

109
Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes DOI

Maria Fasolino,

Gregory W. Schwartz, Abhijeet R. Patil

et al.

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(2), P. 284 - 299

Published: Feb. 28, 2022

Language: Английский

Citations

105