Human regulatory γδT lymphocytes as novel autoimmunity-protective cells: Lessons from alopecia areata DOI Creative Commons
Amos Gilhar, Aviad Keren,

Nyra Goldstein

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Abstract Regulatory T cells control autoimmune diseases (AID). Yet, much less is known about the functions of evolutionarily older Foxp3 + human regulatory γδT (γδTregs). Here, we have explored these in one most common AID, hair loss disorder, alopecia areata (AA). Lesional AA skin showed significantly more γδTreg than non-lesional or healthy skin. Next, investigated how γδTregs impact on experimentally induced scalp xenotransplants SCID/beige mice. PBMC-derived autologous were pre-activated with IL-2, IL-15, and zoledronate in vitro injected intradermally into xenografts before after induction by CD8 vivo. not only prevented development lesions, but also promoted regrowth established lesions xenotransplants, accompanied a reduced perifollicular lymphocytic infiltrate restoration follicle (HF) immune privilege (IP) . We then co-cultured organ-cultured, stressed (MICA-overexpressing) HFs presence/absence pathogenic CD8+/NKG2D that induce HF IP collapse secreting interferon-g, all under conditions. Under ex vivo conditions, mitigated cells, primarily through IL-10 TGF-β1 secretion, enhanced keratinocyte proliferation their apoptosis while preventing premature catagen (= hallmarks). These findings model AID introduce as important lymphocytes invite novel cell-based therapies cell-dependent AIDs characterized such AA.

Language: Английский

The universal effects of low-dose interleukin-2 across 13 autoimmune diseases in a basket clinical trial DOI
Roberta Lorenzon,

Claire Ribet,

Fabien Pitoiset

et al.

Journal of Autoimmunity, Journal Year: 2024, Volume and Issue: 144, P. 103172 - 103172

Published: Feb. 7, 2024

Language: Английский

Citations

19
The absolute number of circulating Treg cells is reduced in difficult-to-treat RA patients and is ameliorated by low-dose IL-2 DOI Creative Commons
Huanhuan Yan,

Xiaoyu Zi,

Huer Yan

et al.

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

Published: Feb. 6, 2025

Circulating regulatory T cells (Tregs) are closely related to immune tolerance and maintenance of homeostasis. Perhaps, there is a unique cell phenotype for difficult-to-treat rheumatoid arthritis (D2T RA). Low-dose interleukin-2 (IL-2) has been considered the treatment autoimmune diseases. This study focused on uniqueness D2T RA lymphocyte subsets feasibility low-dose IL-2 therapy. Participants included 1,042 patients who were divided into three groups according presence or absence their response in last 6 months-new group, treated group-and 339 healthy controls (HCs). A total 381 patients-107, 151, 123 each experimental groups-received [0.5 million international units (MIU) per day, subcutaneous injection from day 1 5]. The absolute numbers peripheral blood detected by flow cytometry (FCM) serum cytokine levels bead array (CBA). number T, CD4+ Treg group was lower than that HC, new, groups. Compared with HC new ratio Th17/Treg increased. treated, had higher HC. negatively correlated disease activity index. could be increased therapy without any side effects. lymphocytes reduced, especially cells, resulting shift balance effector cells/Treg toward which ameliorated obvious

Language: Английский

Citations

0
IL-2/anti-IL-2 complexes attenuates neuroinflammation and neurodegeneration in mice of experimental Parkinson's disease. DOI Creative Commons
Lanxin Li, Weiwei Gao,

Ning Ren

et al.

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 111273 - 111273

Published: Feb. 1, 2025

Language: Английский

Citations

0
The Lasting Impact of IL-2: Approaching 50 Years of Advancing Immune Tolerance, Cancer Immunotherapies, and Autoimmune Diseases DOI

Prajita Paul,

Cherry Choong,

Joseph Heinemann

et al.

Immunological Investigations, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: March 17, 2025

Background The discovery of interleukin-2 (IL-2) and its receptor (IL-2R) almost 50 years ago revolutionized immunology, marking a pivotal moment in understanding T cell biology immune regulation. Initially identified as growth factor, IL-2 unveiled critical insights into cytokine-mediated proliferation differentiation.

Language: Английский

Citations

0
Glucagon-like peptide-1 agonism in combination with low-dose interleukin 2 enhances regulatory T cell suppressive function in vitro DOI
Aaron D. Thome,

Jason R. Thonhoff,

Jinghong Wang

et al.

NeuroImmune Pharmacology and Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract Objectives Dysregulated immune responses are characterized by pro-inflammatory activated myeloid cells that impair regulatory T cell (Treg) function and drive chronic inflammatory, autoimmune, neurodegenerative diseases. Suppression of activation provides the potential to enhance Treg neuroprotective functions. Individually, low-dose interleukin-2 (LD-IL2) glucagon-like peptide-1 receptor agonists (GLP-1RA) demonstrate promising immunomodulatory effects in preclinical models clinical trials. The current study evaluates combination these therapeutic modalities suppress cells, suppressive functions, modulate proliferation vitro. Methods Peripheral monocytes, Tregs, responder (Tresps) from healthy donors were isolated co-cultured with single dosing LD-IL2 (COYA 301) GLP-1RA (Semaglutide, Exendin-4). Pro-inflammatory stimulated lipopolysaccharide (LPS) interferon-gamma (IFN-γ). function, cytokines, inflammatory transcripts, Tresp suppression assessed vitro culture. Results Combination treatment COYA 301 enhanced IL-6 production reduced transcripts TNF, increased anti-inflammatory marker ARG1. was more effectively suppressed than either agent alone. Tregs treated exhibited FOXP3, IL2RA/CD25, CTLA-4 expression, along anti-apoptotic BCL-2 pro-apoptotic BAX transcripts. Conclusions additive enhancing reducing signaling, promoting survival. These findings support this

Language: Английский

Citations

0
Oxytocin‐Mediate Modulation of Splenic Immunosuppression in Chronic Social Stress Through Neuroendocrine Pathways DOI Creative Commons
Yi‐Shu Zhang, Haichao Chen, Jia‐Xin Cao

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

Abstract Chronic social stress (CSS) is a significant public health challenge that negatively impacts behavior and immune function through brain‐spleen interactions. Oxytocin (OT), neuropeptide critical for regulation, upregulated during CSS, though its underlying mechanisms remain unclear. This study investigates the role of OT in splenic modulation using murine model CSS. Behavioral evaluations, serum oxytocin quantification, immunophenotypic analysis were performed. Splenic denervation confirmed OT’s neuromodulatory role, whereas OTR antagonism revealed endocrine function. CSS‐induced elevation was associated with immunosuppression, characterized by increased Foxp3⁺ regulatory T cells reduced CD4⁺ CD19⁺ B cells. also modulated macrophage polarization, inhibiting M1‐like (pro‐inflammatory) enhancing M2‐like (anti‐inflammatory) phenotypes. Denervation or pharmacological blockade signaling partly reversed immunosuppression but adversely affected survival CSS‐exposed mice. Additionally, mice's response to defeat, as shown decreased avoidance behavior. These findings suggest OT‐mediated likely represents compensatory mechanism chronic stress. Targeting OT–immune axis could offer innovative therapeutic approaches stress‐associated disorders restoring homeostasis while maintaining behavioral integrity.

Language: Английский

Citations

0
The effects of low-dose IL-2 on Th17/Treg cell imbalance in primary biliary cholangitis mouse models DOI Creative Commons
Zilong Wang, Zhicheng Liu,

Jiarui Zheng

et al.

BMC Gastroenterology, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 26, 2024

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets patients with autoimmune diseases. Hence, the present study aimed to examine effects and mechanism low-dose mouse models. models were induced female C57BL/6 mice by two immunizations 2OA-BSA at two-week intervals, poly I: C every three days. divided into treated untreated groups was injected different time points. Th17 Tregs analyzed flow cytometry, related cytokines ELISA. Liver histopathology examined H&E immunohistochemical staining. Twelve weeks after modeling, serum AMA positive ALP significantly increased (P<0.05). pathology showed lymphocyte infiltration portal area, damage, reactive proliferation small bile duct cytometric models, decreased Treg cells, ratio (P < 0.05). After intervention, biochemical index pathologies improvement 12 weeks. Besides, recovered. Public database mining that differentiation may contribute poor response improve biochemistry reversing suggesting it be potential therapeutic target for PBC.

Language: Английский

Citations

2
Vaccines against autoimmune diseases DOI

Divya Jyothi Madipally,

Janna R. Pathi

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 203 - 239

Published: Jan. 1, 2024

Citations

1
Rheumatoid arthritis: a complex tale of autoimmune hypersensitivity DOI Creative Commons

Jihye Heo,

Soohyun Heo,

Joo Ri Kang

et al.

Exploration of Immunology, Journal Year: 2024, Volume and Issue: unknown, P. 358 - 375

Published: June 20, 2024

Rheumatoid arthritis (RA) is a complex autoimmune disorder characterized by spectrum of hypersensitivity reactions, encompassing Type II, III, and IV responses. Firstly, RA marked II reactions driven autoantibodies, such as rheumatoid factor (RF) anti-(cyclic) citrullinated protein antibodies (ACPAs). These autoantibodies serve not only serological markers for but also actively participate in inflammation, bone erosion, clinical outcomes, with concurrent activation the complement system involving C1q, C3, C5 components specifically linked to progression damage. Secondly, exhibits traits III hypersensitivity, formation immune complexes inciting inflammatory reactions. Immunoglobulin G (IgG) like RF ACPA play pivotal roles ensuing demonstrates propelled CD4+ T cells, helper 1 (Th1) Th17 subsets. Th1 cells release interferon (IFN)-γ, promoting proinflammatory cytokines, while secrete IL-17, IL-22, granulocyte-macrophage colony-stimulating (GM-CSF), contributing synovial cartilage damage, angiogenesis. concurrently features hypersensitivity. It crucial comprehend presence interplay responses specific cell subsets create precise efficient therapeutic approaches management this incapacitating condition. Thus, review, we aim provide comprehensive overview RA.

Language: Английский

Citations

0
A two-sample Mendelian randomization study to explore the causal relationship between immune inflammatory factors and systemic lupus erythematosus DOI Creative Commons
Mingying Zhang, Junbing He, Zhibin Lin

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 26, 2024

Abstract Background The effect of inflammatory factors on systemic lupus erythematosus has now been widely recognized, however, causal relationship between and SLE pathogenesis is uncertain. Methods Aggregate statistics for each factor immune feature are publicly available from the Genome-Wide Association Study catalog. This dataset includes a total 91 731 phenotypes, initial GWAS features used data 3,757 individuals European descent. Correlations were examined after adjusting covariates. overall impact can be dissected into direct indirect effects. inverse variance weighing method standard MR analysis. Sensitivity analysis was also perform to optimize reliability accuracy results. Results Potential association identified levels caspase 8, fractalkine, IL-2, signaling lymphocytic activation molecule (SLAM), T cell surface glycoprotein CD8 isoform, TNF ligand superfamily member 14, receptor 9 (TNFRSF9) occurrence.(P<0.05). Among 28 analyzed, Nine nineteen exhibited positive negative with SLE. When selecting most significant P-values in IL-2 significantly associated increased risk ( P = 0.029, β 0.41, OR 1.508, 95% CI 1.040–2.185). Total 0.410, breakdown this yielded an 0.024, mediated through percentage CD25hi CD45RA− CD4+ Tregs, 0.386 mediation rate 6.05%. MR-Egger intercept test showed that there no horizontal pleiotropy (P > 0.05) among IVs. supported validity Conclusions These study associations Caspase SLAM, TNFRSF9 etiology Immune probably involved process. Our suggested may new regulatory mechanism likely potential therapeutic targets

Language: Английский

Citations

0