ThymoSpheres culture: A model to study human polyclonal unconventional T cells DOI Creative Commons
Lore Billiet, Hanne Jansen, Melissa Pille

et al.

European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(12)

Published: Sept. 9, 2024

In vitro cultures remain crucial for studying the fundamental mechanisms of human T-cell development. Here, we introduce a novel in cultivation system based on ThymoSpheres (TS): dense spheroids consisting DLL4-expressing stromal cells and hematopoietic precursor cells, absence thymic epithelial cells. These are subsequently cultured at air-liquid interphase. TS generate large numbers mature T easy to manipulate, scalable, can be repeatably sampled monitor differentiation. The generated from primary were extensively characterized using single-cell RNA combined receptor (TCR) sequencing. predominantly CD8α exhibit transcriptional TCR CDR3 characteristics similar recently described polyclonal αβ unconventional cell (UTC) lineage. This includes expression hallmark genes associated with agonist selection, such as IKZF2 (Helios), various natural killer receptors. repertoire these UTCs is enriched CDR3-associated autoreactive features early rearrangements TCR-α chain. conclusion, offer an intriguing platform study development this UTC lineage its inducing selection mechanisms.

Language: Английский

MAIT cells and the microbiome DOI Creative Commons
Maisha Jabeen, Timothy S.C. Hinks

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 23, 2023

Mucosal associated invariant T (MAIT) cells are innate-like lymphocytes, strikingly enriched at mucosal surfaces and characterized by a semi-invariant αβ cell receptor (TCR) recognizing microbial derived intermediates of riboflavin synthesis presented the MHC-Ib molecule MR1. At barrier sites MAIT occupy prime position for interaction with commensal microorganisms, comprising microbiota. The microbiota is rich source antigens required in early life to promote intra-thymic development sustain life-long population tissue resident cells. A symbiotic relationship thought be maintained health whereby microbes maturation homeostasis, turn can engage TCR-dependent "tissue repair" program presence organisms conducive sustaining function integrity community. activation induced MR1-TCR dependent manner or through independent mechanisms

Language: Английский

Citations

27
TSLP pretreatment inhibits M1 macrophage polarization and attenuates LPS-induced iNKT cell-dependent acute lung injury DOI Creative Commons
Ting Zhou, Ziyao Zhang,

Yawen Zhan

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 23, 2025

Introduction Sepsis associated acute respiratory distress syndrome (ARDS), is a life-threatening condition characterized by severe pulmonary inflammation. Previous research has suggested that allergic immune diseases are with lower risk of sepsis. Therefore, we hypothesized certain molecules involved in type 2 inflammation beneficial for the outcome sepsis ARDS. Thymic stromal lymphopoietin (TSLP) known to promote Th2 responses disease, however, its role ARDS remains limited. Methods To investigate TSLP lung injury, administered exogenous recombinant wild-type mice, followed lipopolysaccharide (LPS) challenge. At 24 hours post-treatment, bronchoalveolar lavage fluid (BALF) and tissues were collected analysis. The ratio, number, phenotype, function cells cytokine levels measured. Additionally, murine bone marrow-derived macrophages (BMDMs) prepared stimulated LPS further verify our findings experimentally. explore molecular mechanisms TSLP’s effect, analysis transcriptome sequencing single-cell subsequent experiments performed. Results In LPS-induced injury models, pretreatment significantly alleviated suppressed inflammatory cytokines secretion, reduced neutrophils infiltration. addition, treatment inhibited M1 macrophage polarization promoted M2 differentiation. Transcriptome IFN-γ as potential target TSLP, showed innate like T important source IFN-γ. Consistently, flow cytometry proportion IFN-γ-producing iNKT was decreased administration model. Intriguingly, Jα18 −/− which completely deficient invariant natural killer (iNKT) cells, exhibited not only less but also notably higher degree anti-inflammatory Arg1 + infiltration when compared their LPS-sensitized counterparts. Conclusions These underscore crucial regulation sepsis-associated demonstrate clinical value both predictive biomarker early detection therapeutic intervention.

Language: Английский

Citations

0
MAIT cells exacerbate colonic inflammation in a genetically diverse murine model of spontaneous colitis DOI Creative Commons
Liyen Loh, David J. Orlicky,

Andrea Spengler

et al.

Mucosal Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Markers and makers of NKT17 cells DOI Creative Commons
Nurçin Liman, Jung‐Hyun Park

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(6), P. 1090 - 1098

Published: June 1, 2023

Abstract Invariant natural killer T ( i NKT) cells are thymus-generated innate-like αβ that undergo terminal differentiation in the thymus. Such a developmental pathway differs from of conventional cells, which generated thymus but complete their functional maturation peripheral tissues. Multiple subsets NKT have been described, among IL-17-producing commonly referred to as NKT17 cells. IL-17 is considered proinflammatory cytokine can play both protective and pathogenic roles has implicated key regulatory factor many disease settings. Akin other subsets, acquire effector function during thymic development. However, cellular mechanisms drive subset specification, how general prior antigen encounter, remain largely unknown. Considering all express canonical Vα14-Jα18 TCRα chain display same ligand specificity, i.e., glycolipid antigens context nonclassical MHC-I molecule CD1d, conundrum explaining cell specification determined. Mapping molecular circuitry differentiation, combined with discovery markers identify provided new insights into The current review aims highlight recent advances our understanding development place these findings larger differentiation.

Language: Английский

Citations

9
Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models DOI Creative Commons
Liyen Loh, Salomé Carcy, S. Harsha Krovi

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114705 - 114705

Published: Sept. 1, 2024

Language: Английский

Citations

3
Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation DOI Creative Commons
В. К. Карнаухов, Anne‐Laure Le Gac, Linda Bilonda Mutala

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(14)

Published: March 26, 2024

How T-cell receptor (TCR) characteristics determine subset commitment during development is still unclear. Here, we addressed this question for innate-like T cells, mucosal-associated invariant (MAIT) and natural killer (iNKT) cells. MAIT iNKT cells have similar developmental paths, leading in mice to two effector subsets, cytotoxic (MAIT1/iNKT1) IL17-secreting (MAIT17/iNKT17). For iNKT1 vs iNKT17 fate choice, an instructive role TCR affinity was proposed but recent data argue against model. Herein, examined through scRNAseq repertoire analysis. In our dataset of thymic found pairs clones with identical amino acid sequences originating from distinct precursors, one which committed MAIT1 the other MAIT17 fates. Quantitative silico simulations indicated that number such cases best explained by lineage choice being independent characteristics. Comparison features clonotypes demonstrated subsets cannot be distinguished based on sequence. To pinpoint stage associated sublineage proliferation takes place both before after commitment. Altogether, propose a model cell noncommitted, intermediate-stage undergo first round proliferation, followed characteristics-independent or lineage, additional proliferation. Reanalyzing published dataset, showed also relevant development.

Language: Английский

Citations

2
Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models DOI Creative Commons
Liyen Loh, Salomé Carcy, S. Harsha Krovi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 8, 2023

The "innate-like" T cell compartment, known as

Language: Английский

Citations

4
Intestinal mucosal immunity and type 1 diabetes: Non‐negligible communication between gut and pancreas DOI Creative Commons

Ruonan Liu,

Jing Zhang, Si Chen

et al.

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Abstract Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T cell‐mediated pancreatic β cell loss, resulting in lifelong absolute insulin deficiency and hyperglycaemia. Environmental factors are recognized as key contributor to the development of T1D, with gut serving primary interface for environmental stimuli. Recent studies have revealed that alterations intestinal microenvironment profoundly affect host immune responses, contributing aetiology pathogenesis T1D. However, dominant cells underlying mechanisms remain incompletely elucidated. In this review, we provide an overview possible mucosal system underpin shedding light on roles both non‐classical classical Our goal gain insights into how modulating these components may hold potential implications T1D prevention novel perspectives immune‐mediated therapy.

Language: Английский

Citations

1
Extracellular Vesicle-Based SARS-CoV-2 Vaccine DOI Creative Commons

Yasunari Matsuzaka,

Ryu Yashiro

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 539 - 539

Published: Feb. 24, 2023

Messenger ribonucleic acid (RNA) vaccines are mainly used as SARS-CoV-2 vaccines. Despite several issues concerning storage, stability, effective period, and side effects, viral vector widely for the prevention treatment of various diseases. Recently, vector-encapsulated extracellular vesicles (EVs) have been suggested useful tools, owing to their safety ability escape from neutral antibodies. Herein, we summarize possible cellular mechanisms underlying EV-based

Language: Английский

Citations

3
MAIT cells drive chronic inflammation in a genetically diverse murine model of spontaneous colitis DOI Open Access
Liyen Loh, David J. Orlicky,

Andrea Spengler

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 1, 2023

Abstract Background & aims Lymphocytes that produce IL-17 can confer protective immunity during infections by pathogens, yet their involvement in inflammatory diseases is a subject of debate. Although these cells may perpetuate inflammation, resulting tissue damage, they are also capable contributing directly or indirectly to repair, thus necessitating more detailed investigation. Mucosal-Associated-Invariant-T (MAIT) innate-like T cells, acquiring type III phenotype the thymus. Here, we dissected role MAIT vivo using spontaneous colitis model genetically diverse mouse strain. Methods Multiparameter spectral flow cytometry and scRNAseq were used characterize immune cell dynamics transcriptomic signatures respectively, collaborative-cross strain, CC011/Unc CC011/Unc- Traj33 -/- . Results In contrast many conventional laboratory strains, CC011 strain harbors high baseline population cells. We observed an age-related increase colonic Th17 regulatory neutrophils, which paralleled development colitis. This progression manifested histological traits reminiscent human IBD. The analysis from revealed activation profile consistent with milieu, marked enhanced type-III response. Notably, IL-17A was abundantly secreted colons afflicted mice. Conversely, cell-deficient CC011-Traj33−/− mice, there notable absence significant histopathology. Furthermore, myeloperoxidase staining indicated substantial decrease neutrophils. Conclusions Our findings suggest play pivotal modulating severity intestinal pathology, potentially orchestrating process driving accumulation neutrophils within environment.

Language: Английский

Citations

3