T-cell exhaustion in immune-mediated inflammatory diseases: New implications for immunotherapy DOI Creative Commons

Zhanyan Gao,

Yang Feng, Jinhua Xu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 23, 2022

Immune-mediated inflammatory diseases(IMIDs) are referred to as highly disabling chronic diseases affecting different organs and systems. Inappropriate or excessive immune responses with inflammation typical manifestations. Usually in patients infection cancer, due long-term exposure persistent antigens microenvironment, T-cells continuously stimulated gradually differentiate into an exhausted state. Exhausted lose effector function characteristics of memory T-cells. However, existing studies have found that not only present the tumor environment, but also autoimmunity, associated better prognosis IMIDs. This suggests new prospects for application this reversible process T-cell exhaustion treatment IMID. review will focus on research progress several IMIDs its potential diagnosis

Language: Английский

Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus DOI
Calvin Law, Vanessa Sue Wacleche, Ye Cao

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8022), P. 857 - 866

Published: July 10, 2024

Language: Английский

Citations

25
PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus DOI Creative Commons
John Tchen, Quentin Simon, Léa Chapart

et al.

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

Published: April 22, 2024

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production promoted autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody and progression through mechanisms that remain to be defined. Here, we provide evidence for a direct functional relationship between TFH cells during both humans mice. PD-L1 upregulation on IL-4 are associated with TFH2 cell expansions activity. Pathogenic accumulation, maintenance, function SLO were dependent basophils, which induced transcriptional program allowing differentiation function. Our study establishes mechanistic link promotes nephritis.

Language: Английский

Citations

17
RSAD2: A pathogenic interferon-stimulated gene at the maternal-fetal interface of patients with systemic lupus erythematosus DOI Creative Commons
Xiaoyu Ding,

Yonggang Zhou,

Xiaofeng Qiu

et al.

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 101974 - 101974

Published: Feb. 1, 2025

Pregnancy disorders in patients with autoimmune diseases or viral infections are often associated an excessive response of type I interferons. We identify radical S-adenosyl methionine domain containing 2 (RSAD2) as a pathogenic interferon-stimulated gene (ISG) pregnancy complications systemic lupus erythematosus (SLE). The increased expression RSAD2 mainly occurs macrophages and structural cell populations at the maternal-fetal interface pregnant SLE. elevation leads to accumulation diacylglycerol lipids placenta, impairing necessary vascular development for fetus. Depletion Rsad2 mice models exposed interferon inducers significantly reduces lipid accumulation, injury, embryo disorders. An inhibitor, L-chicoric acid (LCA), alleviates damage, improving outcomes SLE-induced spontaneous mouse models. This study proposes potential targeting improve individuals heightened response.

Language: Английский

Citations

3
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
Helix-Guarded Molecular Clips for Cell-Free DNA Scavenging and Treatment of Systemic Lupus Erythematosus DOI
Yang Zhou, Huan Ye, Yi Yu

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Immune disorders induced by cell-free DNA (cfDNA) account for the incidence and deterioration of systemic lupus erythematosus (SLE). Scavenging cfDNA using cationic polymers represents a promising modality SLE management. However, they bind mainly via electrostatic interaction, which would result in an undesired discharge captured upon competitive replacement negatively charged serum/intracellular components. Inspired natural recognition mechanism biomacromolecules spatial matching, we herein developed library dendrimer-templated, spherical, α-helical, guanidine-rich polypeptides as molecular clips scavenging. Upon optimization polypeptide length density on dendrimer surface, top-performing G3-8 was identified, could tightly confine within cavity between adjacent, rod-like α-helices. As thus, helical but not random-coiled analogue D,L-G3-8 enabled robust scavenging under serum-rich conditions to inhibit TLR9 activation inflammation. In mice, i.v. injected efficiently prevented organ failure inhibited inflammation cfDNA. This study provides enlightened strategy stably scavenge may shift current paradigm

Language: Английский

Citations

2
Gluconolactone restores immune regulation and alleviates skin inflammation in lupus-prone mice and in patients with cutaneous lupus DOI Open Access
Wei Li, Antonios G.A. Kolios, Wenliang Pan

et al.

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(786)

Published: Feb. 19, 2025

Systemic lupus erythematosus (SLE) is characterized by dysfunctional regulatory T cells (T regs ). We previously showed that protein phosphatase 2A (PP2A) plays a critical role in maintaining the suppressive function of . Here, we analyzed phosphoproteomics and metabolomics data from PP2A–wild type PP2A-deficient demonstrated PP2A regulates reg through pentose phosphate pathway (PPP). Furthermore, proved PPP metabolite gluconolactone (GDL) enhances vitro induced (i)T differentiation promoting forkhead box 3 phosphorylated signal transducer activator transcription 5 expression inhibits helper 17 H 17) murine cells. In short-term imiquimod-induced autoimmunity mice, treatment with GDL alleviates inflammation inhibiting promotes skin lesions MRL. lpr lupus-prone mice vivo. It also ex vivo experiments using patients SLE. Last, suffering cutaneous erythematosus, topical application GDL-containing cream controlled improved clinical histologic appearance within 2 weeks. Together, have identified as mechanistically it restores immune regulation inducing should be considered approach for inflammatory autoimmune diseases.

Language: Английский

Citations

2
Interleukin-2 and regulatory T cells in rheumatic diseases DOI
Antonios G.A. Kolios, George C. Tsokos, David Klatzmann

et al.

Nature Reviews Rheumatology, Journal Year: 2021, Volume and Issue: 17(12), P. 749 - 766

Published: Nov. 2, 2021

Language: Английский

Citations

87
Interleukin-35: Structure, Function and Its Impact on Immune-Related Diseases DOI
Ye Cheng, Hiroshi Yano, Creg J. Workman

et al.

Journal of Interferon & Cytokine Research, Journal Year: 2021, Volume and Issue: 41(11), P. 391 - 406

Published: Nov. 1, 2021

The balance between inflammatory and anti-inflammatory immune responses is maintained through immunoregulatory cell populations immunosuppressive cytokines. Interleukin-35 (IL-35), an inhibitory cytokine that belongs to the IL-12 family, capable of potently suppressing T proliferation inducing IL-35-producing induced regulatory cells (iTr35) limit responses. Over past decade, a growing number studies have indicated IL-35 plays important role in controlling immune-related disorders, including autoimmune diseases, infectious cancer. In this review, we summarize current knowledge about biology its contribution different discuss potential barriers harnessing as clinical biomarker or immunotherapy.

Language: Английский

Citations

82
T Cell Abnormalities in the Pathogenesis of Systemic Lupus Erythematosus: an Update DOI
Ping-Min Chen, George C. Tsokos

Current Rheumatology Reports, Journal Year: 2021, Volume and Issue: 23(2)

Published: Jan. 29, 2021

Language: Английский

Citations

75
Toll-Like Receptors Gene Polymorphisms in Autoimmune Disease DOI Creative Commons
Yingchi Zhang, Jia Liu,

Changlun Wang

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: April 26, 2021

Toll-like receptors (TLRs) are important initiators of the immune response, both innate and acquired. Evidence suggests that gene polymorphisms within TLRs cause malfunctions certain key TLR-related signaling pathways, which subsequently increases risk autoimmune diseases. We illustrate discuss current findings on role receptor in numerous diseases this review, such as type 1 diabetes mellitus, Graves’ disease, rheumatoid arthritis, systemic lupus erythematosus multiple sclerosis. The study genetic variation different populations has shown a complex interaction between immunity environmental factors. This TLR affect susceptibility to differently various populations. identification can expand our understanding pathogenesis diseases, will guide effective medical management provide insight into prognosis advanced treatments.

Language: Английский

Citations

71