The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis—A Systematic Review

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2589 - 2589

Опубликована: Фев. 23, 2024

Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple remains an incurable disease, management MS predominantly focuses on reducing relapses decelerating progression both physical cognitive decline. The continuous autoimmune process modulated cytokines seems to be vital contributing factor development relapse sclerosis. This review sought summarize role selected interleukins in pathogenesis advancement MS. Patients with active disease phase seem exhibit increased serum level IL-2, IL-4, IL-6, IL-13, IL-17, IL-21, IL-22 IL-33 compared healthy controls patients remission, while IL-10 appears have beneficial impact preventing disease. Despite being usually associated proinflammatory activity, several studies additionally recognized neuroprotective IL-33. Moreover, gene polymorphisms IL-2R, IL-13 were identified as possible risk related development. Treatment strategies either target or utilize these rather promising, but more comprehensive research necessary gain clearer understanding how precisely affect progression.

Язык: Английский

---

Emerging roles of astrocytes as immune effectors in the central nervous system

Trends in Immunology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

---

IL-4, TSLP and IL-31 Cytokine Profiles as Related to Psychometric Measures in Patients with Mastocytosis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 529 - 529

Опубликована: Янв. 9, 2025

Mastocytosis is a rare neoplastic disease of the bone marrow. Common symptoms like urticaria, diarrhea, bronchspasm and flushing are caused by mast cell degranulation mostly based on mediator release Th2 type inflammation that occurs frequently in these patients. Psychological disorders more prevalent patients with systemic mastocytosis, though little known about mechanism behind this. The aim study was to investigate cytokine (IL-4, TSLP, IL-31 IL-33) profile mastocytosis relation classic psychometric measures cognition distress symptoms.In total, 115 diagnosed were enrolled. Mini-Mental State Examination (MMSE) performed for all subjects. Other variables: Quality life mood assessment commonly used certified rater—the Hamilton-17 Depression Scale, Pruritus Visual Analog Score, serum tryptase concentration marrow biopsy results (archival) also analyzed/included. Serum concentrations IL-4, IL-33 analyzed as primary outcomes. For comparison continuous variables linear regression used. mean MMSE result 27.9. Regression analysis did not reveal significant correlation between IL-4 (p = 0.82), 0.24) TSLP 0.37) MMSE. resulted 0 (was detected). No effect observed other endpoints well. One four presents cognitive decline. This impairment does correlate Il-4, nor protein concentrations.

Язык: Английский

---

Malignant JAK-signaling: at the interface of inflammation and malignant transformation

Leukemia, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Abstract The JAK pathway is central to mammalian cell communication, characterized by rapid responses, receptor versatility, and fine-tuned regulation. It involves Janus kinases (JAK1, JAK2, JAK3, TYK2), which are activated when natural ligands bind receptors, leading autophosphorylation activation of STAT transcription factors [1, 2]. JAK-dependent signaling plays a pivotal role in coordinating communication networks across broad spectrum biological systems including development, immune growth, differentiation. JAKs frequently mutated the aging hematopoietic system [3, 4] cancers [5]. Thus, dysregulation results various diseases, disorders. binding extracellular class I II cytokine receptors initiates critical cascade through (JAKs). Upon ligand engagement, become phosphorylate specific tyrosine residues on receptor, creating docking sites for signal transducer activator (STAT) proteins. Subsequent JAK-mediated phosphorylation STATs enables their dimerization nuclear translocation, where they function as modulate gene expression. Under physiological conditions, JAK-signaling tightly regulated mechanism that governs cellular responses external cues, such cytokines growth factors, ensuring homeostasis maintaining functional integrity tissues organs. Highly defined regulation essential balancing inflammatory stimuli signals, thus safeguarding tissue health. In contrast, dysregulated chronic inflammation unrestrained proliferation associated with diseases. Understanding qualitative quantitative differences at interface physiologic its aberrant disease crucial development targeted therapies precisely tune this target pathologic patterns while leaving homeostatic processes largely unaffected. Consequently, pharmaceutical research has drug approval several substances different selectivity profiles towards individual JAKs. Yet, precise impact inhibitor complex interplay modules within normal malignant cells remains incompletely understood. review, we summarize current knowledge health highlight recent advances future directions field.

Язык: Английский

---

Inflammatory and anti-inflammatory cytokines bidirectionally modulate amygdala circuits regulating anxiety

Cell, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

---

Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models

Oxford Open Neuroscience, Год журнала: 2024, Номер 3

Опубликована: Янв. 1, 2024

Autism spectrum disorder (ASD) affects 1 in 36 people and is more often diagnosed males than females. Core features of ASD are impaired social interactions, repetitive behaviors deficits verbal communication. a highly heterogeneous heritable disorder, yet its underlying genetic causes account only for up to 80% the cases. Hence, subset cases could be influenced by environmental risk factors. Maternal immune activation (MIA) response inflammation during pregnancy, which can lead increased inflammatory signals fetus. Inflammatory cross placenta blood brain barriers affecting fetal development. Epidemiological animal studies suggest that MIA contribute etiology. However, human mechanistic have been hindered lack experimental systems replicate impact Therefore, mechanisms altered pre-natal development, underlie pathogenesis largely understudied. The advent cellular models with induced pluripotent stem cell (iPSC) organoid technology closing this gap knowledge providing both access molecular manipulations culturing capability tissue would otherwise inaccessible. We present an overview multiple levels evidence from clinical, epidemiological, provide potential link between higher inflammation. More importantly, we discuss how cell-derived may constitute ideal system mechanistically interrogate effect early stages

Язык: Английский

---

Navigating the Neuroimmunomodulation Frontier: Pioneering Approaches and Promising Horizons—A Comprehensive Review

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9695 - 9695

Опубликована: Сен. 7, 2024

The research in neuroimmunomodulation aims to shed light on the complex relationships that exist between immune and neurological systems how they affect human body. This multidisciplinary field focuses way responses are influenced by brain activity neural function is impacted immunological signaling. provides important insights into a range of medical disorders. Targeting both pathways, neuroimmunomodulatory approaches used clinical pain management address chronic pain. Pharmacological therapies aim modulate neuroimmune interactions reduce inflammation. Furthermore, bioelectronic techniques like vagus nerve stimulation offer non-invasive control these systems, while neuromodulation transcranial magnetic modify neuronal Within context aging, analyzes ways which alterations brought aging contribute cognitive decline neurodegenerative illnesses. Restoring homeostasis through strategies shows promise reducing age-related decline. Research mood disorders dysregulation relates illnesses including anxiety depression. Immune system fluctuations increasingly recognized for their impact function, leading novel treatments target interactions. review emphasizes interdisciplinary cooperation continuous necessary better understand relationship systems.

Язык: Английский

---

Inhibition of NADPH oxidase 2 enhances resistance to viral neuroinflammation by facilitating M1-polarization of macrophages at the extraneural tissues

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Май 2, 2024

Abstract Background Macrophages play a pivotal role in the regulation of Japanese encephalitis (JE), severe neuroinflammation central nervous system (CNS) following infection with JE virus (JEV). are known for their heterogeneity, polarizing into M1 or M2 phenotypes context various immunopathological diseases. A comprehensive understanding macrophage polarization and its relevance to progression holds significant promise advancing control therapeutic strategies. Methods To elucidate NADPH oxidase-derived reactive oxygen species (ROS) progression, we assessed viral load, accumulation, cytokine production WT oxidase 2 (NOX2)-deficient mice using murine model. Additionally, employed bone marrow (BM) cell-derived macrophages delineate ROS-mediated by ROS JEV infection. Results NOX2-deficient exhibited increased resistance rather than heightened susceptibility, driven polarization. These displayed reduced loads peripheral lymphoid tissues CNS, along diminished infiltration inflammatory cells thereby resulting attenuated neuroinflammation. enhanced JEV-specific Th1 CD4 + CD8 T cell responses accumulation producing IL-12p40 iNOS inflamed extraneural tissues. Mechanistic investigations revealed that more pronounced differentiation response infection, leading suppression replication. Importantly, administration H O generated NOX2 was shown inhibit Finally, oral scavenger, butylated hydroxyanisole (BHA), bolstered both facilitated macrophages. Conclusion In light our results, it is suggested undermining replication within tissues, primarily suppressing Subsequently, this leads an augmentation load invading facilitating progression. Hence, findings ultimately underscore significance initiated

Язык: Английский

---

Immune Dysregulation in Obesity

Annual Review of Pathology Mechanisms of Disease, Год журнала: 2025, Номер 20(1), С. 483 - 509

Опубликована: Янв. 24, 2025

The immune system plays fundamental roles in maintaining physiological homeostasis. With the increasing prevalence of obesity-a state characterized by chronic inflammation and systemic dyshomeostasis-there is growing scientific clinical interest understanding how obesity reshapes function. In this review, we propose that not merely an altered metabolic but also a fundamentally immunological state. We summarize key seminal recent findings elucidate influences function, spanning its classical role microbial defense, contribution to maladaptive inflammatory diseases such as asthma, impact on antitumor immunity. explore modulates function within tissue parenchyma, with particular focus T cells adipose tissue. Finally, consider areas for future research, including investigation durable aspects even after weight loss, those observed glucagon-like peptide-1 (GLP-1) receptor agonist treatment. Altogether, review emphasizes critical metabolism shaping cell functions, profound implications homeostasis across various contexts.

Язык: Английский

---

CD8+T cells and monocytes were associated with brain alterations in human immunodeficiency virus-infected individuals with cognitive impairment

Brain Research Bulletin, Год журнала: 2025, Номер unknown, С. 111231 - 111231

Опубликована: Янв. 1, 2025

Cognitive impairment (CI) continues to be a concern for people living with HIV-1 (PLWH) in the era of antiretroviral therapy (ART), yet underlying mechanisms remain unclear. We aimed elucidate structural and functional brain alterations peripheral immune profile PLWH CI, as well correlation between them. were divided into CI (n= 30) cognitive normal (CN, n= 59) groups based on Montreal Assessment, underwent multi-modal magnetic resonance imaging. Mass cytometry was utilized cells, while liquid chip technique employed measure plasma levels cytokines chemokines. Spearman analyses conducted analysis. Here, we found that gray matter volume left supramarginal gyrus reduced, ReHo right middle frontal connectivity postcentral enhanced group compared CN group. Additionally, frequencies naïve CD8+T cells (Tn) CD31lowCD8+ Tn significantly correlated gyrus. The amplitude low frequency fluctuations specific region frontal-middle lobe negatively non-classical monocytes (nCM) their subpopulations (CCR2lownCM, CD57lownCM CD127+nCM), positively associated interleukin 25 transforming growth factor-α levels. These findings suggest association immunity abnormalities PLWH, highlighting potential role immune-brain-cognition axis pathogenesis Chinese PLWH.

Язык: Английский

---