Seminars in Immunology, Journal Year: 2023, Volume and Issue: 69, P. 101814 - 101814
Published: Aug. 3, 2023
Language: Английский
Citations
38Stem-like CD4 + T cells in perivascular tertiary lymphoid structures sustain autoimmune vasculitis
Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(712)
Published: Sept. 6, 2023
Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, aneurysm. The disease is often refractory to immunosuppressive therapy progresses over decades as smoldering aortitis. How granulomatous infiltrates in vessel wall are maintained how tissue-infiltrating T cells macrophages replenished unknown. Single-cell whole-tissue transcriptomic studies immune cell populations vasculitic identified a CD4 + population with stem cell–like features. supplying tissue-damaging effector survived tertiary lymphoid structures around adventitial vasa vasora, expressed transcription factor 1 (TCF1), had high proliferative potential, gave rise two populations, Eomesodermin (EOMES) cytotoxic B lymphoma 6 (BCL6) follicular helper-like cells. TCF1 hi expressing interleukin 7 receptor (IL-7R) sustained serial transplantation experiments. Thus, function promote chronicity autonomy autoimmune tissue inflammation. Remission-inducing therapies will require targeting stem-like instead only
Language: Английский
Citations
21A reappraisal of IL-9 in inflammation and cancer
Mucosal Immunology, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
Language: Английский
Citations
6Genes deregulated in giant cell arteritis by Nanostring nCounter gene expression profiling in temporal artery biopsies
RMD Open, Journal Year: 2024, Volume and Issue: 10(3), P. e004600 - e004600
Published: Sept. 1, 2024
Objective To identify differentially expressed genes in temporal artery biopsies (TABs) from patients with giant cell arteritis (GCA) different histological patterns of inflammation: transmural inflammation (TMI) and limited to adventitia (ILA), compared normal TABs without GCA. Methods Expression 770 immune-related was profiled the NanoString nCounter PanCancer Immune Profiling Panel on formalin-fixed paraffin-embedded 42 GCA TMI, 7 ILA non-GCA controls. Results Unsupervised clustering samples revealed two distinct groups: one group, 41/42 TMI other one. showed 31 downregulated 256 upregulated TABs; they displayed 26 187 (>2.0 fold changes adjusted p values <0.05). Gene expression resembled although 38 exhibited >2.0 changes, but these lost statistical significance after Benjamini-Yekutieli correction. Genes encoding TNF superfamily members, immune checkpoints, chemokine receptors, toll-like complement molecules, Fc receptors for IgG antibodies, signalling lymphocytic activation JAK3, STAT1 STAT4 resulted TMI. Conclusions had a transcriptome ILA. The few potentially deregulated were also profiling allowed deepen knowledge pathogenesis.
Language: Английский
Citations
5The Contribution of Innate Immunity in Large-Vessel Vasculitis: Detangling New Pathomechanisms beyond the Onset of Vascular Inflammation
Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 271 - 271
Published: Feb. 1, 2024
Large-vessel vasculitis (LVV) are autoimmune and autoinflammatory diseases focused on vascular inflammation. The central core of the intricate immunological molecular network resides in disruption "privileged immune state" arterial wall. outbreak, initially primed by dendritic cells (DC), is then continuously powered a feed-forward loop intimate cooperation between innate adaptive immunity. If role immunity has been largely elucidated, knowledge critical function LVV still fragile. A growing body evidence strengthened active players their key signaling pathways orchestrating complex pathomechanisms underlying LVV. Besides DC, macrophages crucial culprits development participate across all phases inflammation, culminating vessel wall remodeling. In recent years, variety potential pathogenic actors expanded to include neutrophils, mast cells, soluble mediators, including complement system. Interestingly, new insights have recently linked inflammasome paving way for its Overall, these observations encourage conceptual approach that includes more in-depth study guide future targeted therapies.
Language: Английский
Citations
5Vascular disease persistence in giant cell arteritis: are stromal cells neglected?
Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: unknown, P. ard - 225270
Published: April 29, 2024
Giant cell arteritis (GCA), the most common systemic vasculitis, is characterised by aberrant interactions between infiltrating and resident cells of vessel wall. Ageing breach tolerance are prerequisites for GCA development, resulting in dendritic T-cell dysfunction. Inflammatory cytokines polarise T-cells, activate macrophages synergistically enhance vascular inflammation, providing a loop autoreactivity. These events originate adventitia, commonly regarded as biological epicentre wall, with additional recruitment that infiltrate migrate towards intima. Thus, GCA-vessels exhibit infiltrates across layers, various growth factors amplifying pathogenic process. ineffective repair mechanisms, where dysfunctional smooth muscle fibroblasts phenotypically shift along their lineage colonise While high-dose glucocorticoids broadly suppress these inflammatory events, they cause well known deleterious effects. Despite emerging targeted therapeutics, disease relapse remains common, affecting >50% patients. This may reflect discrepancy local mediators inflammation. Indeed, temporal arteries aortas GCA-patients can show immune-mediated abnormalities, despite treatment induced clinical remission. The mechanisms persistence remain elusive. Studies other chronic diseases point to (and including myofibroblasts) possible orchestrators or even effectors chronicity through immune cells. Here, we critically review contribution stromal pathogenesis analyse molecular which would underpin disease.
Language: Английский
Citations
4Th9-derived IL-9 in autoimmune diseases: An update
Life Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 123720 - 123720
Published: May 1, 2025
Language: Английский
Citations
0Modulation of Immune Cell Functions by CD226 Family Receptors
Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
0Current Insights into Tissue Injury of Giant Cell Arteritis: From Acute Inflammatory Responses towards Inappropriate Tissue Remodeling
Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 430 - 430
Published: Feb. 29, 2024
Giant cell arteritis (GCA) is an autoimmune disease affecting large vessels in patients over 50 years old. It exemplary model of a classic inflammatory disorder with IL-6 playing the leading role. The main comorbidities that may appear acutely or chronically are vascular occlusion to blindness and thoracic aorta aneurysm formation, respectively. tissue bulk expressed as acute chronic delayed-type hypersensitivity reactions, latter being apparent by giant formation. activated monocytes/macrophages associated pronounced Th1 Th17 responses. B-cells neutrophils also participate lesion. However, exact order appearance mechanistic interactions between cells hindered lack cellular molecular information from early stages accurate experimental models. Recently, senescent neutrophil extracellular traps have been described lesions. These structures can remain tissues for prolonged period, potentially favoring responses remodeling. In this review, current advances GCA pathogenesis discussed different phases. Through description these—often overlapping—phases, cells, molecules, small lipid mediators pathogenetic potential described.
Language: Английский
Citations
2Locus of (IL-9) control: IL9 epigenetic regulation in cellular function and human disease
Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(6), P. 1331 - 1339
Published: June 3, 2024
Abstract Interleukin-9 (IL-9) is a multifunctional cytokine with roles in broad cross-section of human diseases. Like many cytokines, IL-9 transcriptionally regulated by group noncoding regulatory elements (REs) surrounding the IL9 gene. These REs modulate transcription forming 3D loops that recruit transcriptional machinery. IL-9-promoting factors (TFs) can bind to increase locus accessibility and permit chromatin looping, or they be recruited already accessible promote transcription. Ample mechanistic genome-wide association studies implicate this interplay between IL-9-modulating TFs cis -REs physiology, homeostasis, disease.
Language: Английский
Citations
2