Peripheral helper T cells, mavericks of peripheral immune responses

International Immunology, Journal Year: 2023, Volume and Issue: 36(1), P. 9 - 16

Published: Oct. 3, 2023

Peripheral helper T (Tph) cells have been established, through intensive efforts to elucidate local immune responses in human rheumatoid arthritis (RA), as a CD4 subset intimately involved acquired immunity peripheral tissues. Initially, Tph were noted population that produces high levels of CXCL13 RA synovial tissues, followed by demonstration their ability help B cells. In contrast follicular (Tfh) cells, do not express the transcription factor BCL6 but molecules such CXCL13, interleukin (IL)-21, and inducible T-cell costimulator (ICOS) Subsequent studies showed are associated with various diseases, including autoimmune infections, malignancies, development early life immunity. This review summarizes phenotype function discusses differentiation diversity conditions.

Language: Английский

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Help me help you: emerging concepts in T follicular helper cell differentiation, identity, and function

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 87, P. 102421 - 102421

Published: April 1, 2024

Effective high-affinity, long-term humoral immunity requires T cell help provided by a subset of differentiated CD4+ cells known as follicular helper (Tfh) cells. Classically, Tfh provide contact-dependent for the generation germinal centers (GCs) in secondary lymphoid organs (SLOs). Recent studies have expanded conventional definition cells, revealing new functions, descriptions subsets, factors regulating differentiation, and roles outside SLO GCs. Together, these data suggest that one is not equivalent to another, helping redefine our understanding their biology.

Language: Английский

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Emerging roles of checkpoint molecules on B cells

Immunological Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: Jan. 17, 2025

Immune checkpoint molecules, including both co-inhibitory molecules and co-stimulatory are known to play critical roles in regulating T-cell responses. During the last decades, immunotherapies targeting these (such as programmed cell death 1 (PD-1), lymphocyte activation gene 3 (LAG-3)) have provided clinical benefits many cancers. It is becoming apparent that not only T cells, but also B cells a capacity express some molecules. These were originally thought be markers for regulatory which produce IL-10, recent studies suggest (especially immunoglobulin mucin domain (TIM-1), immunoreceptor with Ig ITIM domains (TIGIT), PD-1) can regulate intrinsic B-cell functions. Here, we focus on summarize their characteristics, ligands, functions cells.

Language: Английский

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Tph cells are expanded in IgA vasculitis nephritis

Molecular Immunology, Journal Year: 2025, Volume and Issue: 183, P. 12 - 17

Published: May 1, 2025

Language: Английский

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Atypical and non-classical CD45RBlo memory B cells are the majority of circulating SARS-CoV-2 specific B cells following mRNA vaccination or COVID-19

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 9, 2024

Resting memory B cells can be divided into classical or atypical groups, but the heterogenous marker expression on activated makes similar classification difficult. Here, by longitudinal analysis of mass cytometry and CITE-seq data from cohorts with COVID-19, bacterial sepsis, BNT162b2 mRNA vaccine, we observe that resting cell consist CD45RB+ CD45RBlo memory, which latter contains two distinct groups CD11c+ CD23+ non-classical cells. CD45RB levels remain stable in these after activation, thereby enabling tracking plasmablasts derived either Moreover, both COVID-19 patients vaccination, formed majority SARS-CoV2 specific correlated serum antibodies, while are sepsis. Our results thus identify stably expressed exploited to trace their progeny, suggest contribute SARS-CoV-2 infection vaccination.

Language: Английский

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Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: 135(6)

Published: March 16, 2025

Rheumatoid arthritis (RA) is a systemic autoimmune disease currently with no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in at-risk populations prior to clinical onset crucial establishing Here, we applied multimodal single-cell technologies (mass cytometry and CITE-Seq) characterize the immunophenotypes blood from individuals (ARIs) identified through presence of serum antibodies against citrullinated protein antigens (ACPAs) and/or first-degree relative (FDR) status, as compared patients established RA people healthy control group. We significant cell expansions ARIs controls, including CCR2+CD4+ T cells, peripheral helper (Tph) type 1 CXCR5+CD8+ cells. also found that CD15+ classical monocytes were specifically expanded ACPA-negative FDRs, an activated PAX5lo naive B population was ACPA-positive FDRs. Further, uncovered molecular phenotype expressing high levels Th17- Th22-related signature transcripts CCR6, IL23R, KLRB1, CD96, IL22. Our integrated study provides promising approach identify targets improve strategy development for RA.

Language: Английский

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Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis

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

Published: July 4, 2023

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in ‘At-Risk’ populations prior to clinical onset crucial establishing Here, we applied mass cytometry deeply characterize the immunophenotypes blood from At-Risk individuals identified through presence of serum antibodies citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status (n=52), as compared established RA (n=67), and healthy controls (n=48). We significant cell expansions controls, including CCR2+CD4+ T cells, peripheral helper (Tph) type 1 CXCR5+CD8+ cells. also found that CD15+ classical monocytes were specifically expanded ACPA-negative FDRs, an activated PAX5 low naïve B population was ACPA-positive FDRs. Further, developed “RA immunophenotype score” classification method based on degree enrichment states relevant patients. This score significantly distinguished controls. In all, systematically lymphocyte individuals, along immunophenotypic differences among both ACPA+ ACPA-FDR subpopulations. Our model provides promising approach for understanding pathogenesis goal further improve strategies identify novel therapeutic targets.

Language: Английский

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Ginsenoside Rh4 alleviates idiopathic pulmonary fibrosis by enhancing the CXCL9–CXCR3 axis

Food Frontiers, Journal Year: 2024, Volume and Issue: 5(3), P. 1370 - 1386

Published: March 25, 2024

Abstract Idiopathic pulmonary fibrosis (IPF), often likened to a “tumor‐like disease,” proves more lethal than several malignancies. Although prior studies have demonstrated the lung‐protective efficacy of ginsenosides, precise mechanism underlying their alleviative effect on IPF remains elusive. In this study, we validated ginsenoside Rh4 in alleviating and delved into mechanisms. Our data showed that intervention significantly reduced mortality hydroxyproline (HYP) content mice. It also alleviated pathological process by ameliorating phenomena such as alveolar wall thickening induced IPF. addition, vitro cellular experiments confirmed was effective transforming growth factor‐β1‐induced model. Further analysis collagen fiber production deposition while inhibiting coagulation cascade signaling pathway. inhibited epithelial‐mesenchymal transition(EMT) pathway promoting CXCR3‐CXCL9 axis, which ultimately conclusion, our strongly suggest has potential be an innovative prophylactic drug against

Language: Английский

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Occurrence and role of Tph cells in various renal diseases

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Oct. 10, 2024

A new population of peripheral helper T (Tph) cells has been identified and contributed to various autoimmune diseases. Tph can secrete interleukin-21 (IL-21), interferon (IFN) C-X-C motif chemokine ligand 13 (CXCL13) moderate renal disease. Moreover, congregate in huge numbers immerse within inflamed tissue. Compared Tfh cells, express high programmed cell death protein 1 (PD-1), major histocompatibility complex II (MHC-II), C-C receptor 2 (CCR2) 5 (CCR5) but often lack expression the (CXCR5). They display features distinct from other which are uniquely poised promote responses antibody production B pathologically non-lymphoid tissues a key feature cells. In this review, we summarize recent findings on role chronic kidney disease, acute injury, transplantation

Language: Английский

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Virus infection pattern imprinted and diversified the differentiation of T-cell memory in transcription and function

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 9, 2024

Memory T (Tm) cells are a subpopulation of immune with great heterogeneity. Part this diversity came from that were primed different viruses. Understanding the differences among viral-specific Tms will help develop new therapeutic strategies for viral infections.

Language: Английский

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