PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis

Midgley, Angela; Barakat, Deena; Braitch, Manjit; Nichols, Claude E.; Nebozhyn, Mihailo; Edwards, Laura; Fox, Susan C.; Gran, Bruno; Robins, R. A.; Showe, Louise C.; Constantinescu, Cris S.

doi:10.1016/j.imbio.2020.152023

Cited by 10 publications

(3 citation statements)

References 44 publications

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“…An explanation for this result is that IL-17 concentration might be influenced by other cytokines. Previous studies show that when IL-6 concentration reaches a certain level, it can co-form an internal environment with TGF-β to promote Th17 cell differentiation and IL-17 release (53). It is well known that RORt mRNA expression is sparked by TGF-a and IL-6.…”

Section: Discussionmentioning

confidence: 99%

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

Ouyang

et al. 2022

Front. Psychiatry

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BackgroundDysregulation of immunity, such as levels of inflammatory factors, has been regarded as a sign of schizophrenia. Changes in cytokine levels are not only described in the early onset of disease, but also observed in ultra-high risk (UHR) individuals. This study aimed to investigate the potential of cytokines as biomarkers for psychotic disorders and in individuals at UHR of developing a psychotic disorder in the future.MethodsThe Luminex liquid chip technology was used to detect the concentrations of Interferon-gamma (INF-γ), Interleukin (IL)-2, Interleukin (IL)-4, Interleukin (IL)-6, Interleukin (IL)-17, Interleukin-1beta (IL-1β), and Tumor Necrosis Factor-beta (TNF-β) in the plasma of all subjects. Meanwhile, the plasma level of Tumor Necrosis Factor-Alpha (TNF-α) was measured with the enzyme-linked immunosorbent assay (ELISA) kits. Then, the levels of these cytokines were compared among patients with Drug-naïve first-episode schizophrenia (FES; n = 40), UHR population (UHR; n = 49), and healthy controls (HCs; n = 30). Baseline cytokine levels were compared among UHR individuals who later transitioned (UHR-T; n = 14), those who did not transition (UHR-NT; n = 35), and HCs (n = 30).ResultsOur analysis results showed that IL-1β levels were significantly higher in UHR group than HC group (p = 0.015). Meanwhile, TNF-α concentration was significantly increased in FES group compared with HC group (p = 0.027). IL-17 (p = 0.04) and TNF-β (p = 0.008) levels were significantly higher in UHR-T group compared with UHR-NT group.ConclusionIn conclusion, our findings suggest that the immuno-inflammatory activation level is increased in the early stage of psychosis before psychotic conversion and the Drug-naïve FES. IL-1β and TNF-α are the representatives of the specific biomarkers for UHR and FES, respectively. IL-17 and TNF-β may be the potential selective predictive biomarkers for future transition in UHR individuals.

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Section: Discussionmentioning

confidence: 99%

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

Ouyang

et al. 2022

Front. Psychiatry

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“…Overexpression of CCL2 is closely associated with colonic inflammation in inflammatory bowel disease 73 . IL-23 and IL-17 induce platelet-activating factor receptor (PAF-R) expression on activated T cells, which is invoked by PAF binding to PAF-R. PAF-R is co-expressed with IL-17 and similarly regulated with the Th17 markers IL-17A, IL-17F, IL-22, and RORC 74 . Through STAT3, IL-6 and IL-21 promote the expression of RORA and RORC genes encoding RORα and RORγt, respectively, RORγ(t) is an essential regulator of Th17 cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Exploring the hub mechanisms of ischemic stroke based on protein-protein interaction networks related to ischemic stroke and inflammatory bowel disease

Wei

Li²,

Zeng³

et al. 2023

Sci Rep

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Ischemic stroke is highly concerning because it often leads to severe long-term neurological disability. Among clinical trials, ischemic stroke and inflammatory bowel disease interactions have been increasingly reported in recent years. Therefore, using bioinformatics approaches to explore novel protein interactions between them is of interest. We performed this exploratory analysis by using bioinformatics tools such as string to analyze gene data downloaded from NHGRI-GWAS data related to ischemic stroke and inflammatory bowel disease. We constructed a prospective protein interaction network for ischemic stroke and inflammatory bowel disease, identifying cytokine and interleukin-related signaling pathways, Spliceosome, Ubiquitin–Proteasome System (UPS), Thrombus, and Anticoagulation pathways as the crucial biological mechanisms of the network. Furthermore, we also used data-independent acquisition mass spectrometry (DIA-MS) to detect differential protein expression in eight samples, which also suggested that immune system, signal transduction, and hemostasis-related pathways are key signaling pathways. These findings may provide a basis for understanding the interaction between these two states and exploring possible molecular and therapeutic studies in the future.

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“…The interaction between blood platelets and leukocytes generates platelet-activating factor (PAF), which increases BBB permeability by interrupting endothelial junctions [48][49][50]. Similarly, the formation of cellular aggregates increases the production of matrix metalloproteinases (MMPs) by leukocytes, which are generally recognized as significant participants in BBB disruption [51].…”

Section: Complications In Multiple Sclerosis: From Blood-brain Barrie...mentioning

confidence: 99%

Targeting Vascular Impairment, Neuroinflammation, and Oxidative Stress Dynamics with Whole-Body Cryotherapy in Multiple Sclerosis Treatment

Dziedzic,

Maciak,

Miller

et al. 2024

IJMS

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Multiple sclerosis (MS), traditionally perceived as a neurodegenerative disease, exhibits significant vascular alternations, including blood–brain barrier (BBB) disruption, which may predispose patients to increased cardiovascular risks. This vascular dysfunction is intricately linked with the infiltration of immune cells into the central nervous system (CNS), which plays a significant role in perpetuating neuroinflammation. Additionally, oxidative stress serves not only as a byproduct of inflammatory processes but also as an active contributor to neural damage. The synthesis of these multifaceted aspects highlights the importance of understanding their cumulative impact on MS progression. This review reveals that the triad of vascular damage, chronic inflammation, and oxidative imbalance may be considered interdependent processes that exacerbate each other, underscoring the need for holistic and multi-targeted therapeutic approaches in MS management. There is a necessity for reevaluating MS treatment strategies to encompass these overlapping pathologies, offering insights for future research and potential therapeutic interventions. Whole-body cryotherapy (WBCT) emerges as one of the potential avenues for holistic MS management approaches which may alleviate the triad of MS progression factors in multiple ways.

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PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis

Cited by 10 publications

References 44 publications

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

Exploring the hub mechanisms of ischemic stroke based on protein-protein interaction networks related to ischemic stroke and inflammatory bowel disease

Targeting Vascular Impairment, Neuroinflammation, and Oxidative Stress Dynamics with Whole-Body Cryotherapy in Multiple Sclerosis Treatment

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