The IL-2A receptor pathway and its role in lymphocyte differentiation and function

Li, Yuqian; Li, Xue; Geng, X; Zhao, Haiping

doi:10.1016/j.cytogfr.2022.06.004

Cited by 30 publications

(18 citation statements)

References 133 publications

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“…A large proportion of the upregulated immune system-related proteins were associated with innate immune processes, particularly neutrophils, including proteins involved in neutrophil chemotaxis, activation and degranulation such as LBP, CD14, selectins, elafin, and CCL24 [20]. Interestingly, a number of proteins with anti-inflammatory properties, including IL-1RN, IL-2Ra and NF-κ-BIε, were also reported to be upregulated in blood-derived samples [32][33][34]. Additionally, LDL receptor and proprotein convertase subtilisin/kexin type 9 (PCSK9), important players in the cholesterol metabolism, consistently exhibited increased expression [35].…”

Section: Differentially Expressed Proteins In Bloodmentioning

confidence: 99%

Proteins in the Skin and Blood in Patients with Psoriasis: A Systematic Review of Proteomic Studies

Kromann,

Olsson,

Zhang

et al. 2023

Dermatology

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Background: Proteins play a central role in psoriasis as they are involved in the structural phenotypic changes and inflammation that characterize the disease. This systematic review aimed to assess which proteins have been consistently reported as upregulated or downregulated in the skin and blood from patients with psoriasis. Methods: We included proteomic studies reporting differentially expressed proteins (DEPs) in at least one of four predefined comparisons using a standardized procedure to extract and align data. Network analysis of functional protein associations was made with StringApp in Cytoscape. A protocol for this review was registered in the PROSPERO database (ref:CRD42022363226). Results: We identified and assessed 772 studies published between December 2, 1996, and April 28, 2023, among which 30 studies met the inclusion and data availability criteria for analysis that together reported a sum of 5,314 DEPs. The majority of consistently reported upregulated and downregulated proteins were found in lesional versus non-lesional skin (n = 313), followed by lesional versus healthy skin (n = 185), blood from patients with psoriasis versus blood from healthy individuals (n = 140), and non-lesional versus healthy skin (n = 1). Network analysis of upregulated proteins revealed different functional clusters with interleukin (IL)-6, IL-8, IL-17A, C-C motif chemokine (CCL) 20, signal transducer and activator of transcription (STAT) 3, and interferon (IFN)-γ along with less well-studied proteins playing central roles. Some of the reported changes are associated with anti-inflammatory effects. Additionally, the proteomic dysregulation also included antimicrobial peptides, alarmins, angiogenic factors, and proteins related to protein synthesis. Conclusion: Our findings generally support current understandings of the pathological mechanisms in psoriasis. Importantly, some consistent findings have not been discussed before and deserve attention in future research.

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Section: Differentially Expressed Proteins In Bloodmentioning

confidence: 99%

Proteins in the Skin and Blood in Patients with Psoriasis: A Systematic Review of Proteomic Studies

Kromann,

Olsson,

Zhang

et al. 2023

Dermatology

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“…Elevated CD25 expression may support the survival and maintenance of resting Tregs, while CD39 surface expression is involved in the hydrolysis of extracellular ATP, essential for immunosuppressive function. These mechanisms likely play a crucial role in long-term immune homeostasis after stroke ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

Causal effects of immune cell surface antigens and functional outcome after ischemic stroke: a Mendelian randomization study

Sun,

Gui,

Wan

et al. 2024

Front. Immunol.

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ObjectiveWhile observational studies link immune cells with post-stroke functional outcome, the underlying immune mechanisms are not well understood. Immune cell surface antigens are actively involved in the biological behavior of immune cells, investigating immune cell surface antigens could deepen our comprehension of their role and biological processes in stroke recovery. Therefore, we aimed to investigate the immunological basis of stroke outcome by exploring the causal relationship between immune cell surface antigens and functional outcome after ischemic stroke in a Mendelian randomization study.MethodsGenetic variants related to immune cell surface antigens and post-stroke functional outcome were selected for two-sample Mendelian randomization (MR) analysis. 389 fluorescence intensities (MFIs) with surface antigens were included. Inverse variance weighted (IVW) modeling was used as the primary MR method to estimate the causal effect of exposure on the outcome, followed by several alternative methods and sensitivity analyses. Additional analysis of the association between immune cell surface antigens and risk of ischemic stroke for assessment of collider bias.ResultsWe found that suggestive associations between CD20 on switched memory B cell (OR = 1.16, 95% CI: 1.01-1.34, p = 0.036) and PDL-1 on monocyte (OR = 1.32, 95% CI: 1.04-1.66, p = 0.022) and poor post-stroke functional outcome, whereas CD25 on CD39+ resting Treg (OR = 0.77, 95% CI: 0.62-0.96, p = 0.017) was suggestively associated with good post-stroke functional outcome.ConclusionThe elevated CD20 on switched memory B cell, PDL-1 on monocyte, and CD25 on CD39+ resting Treg may be novel biomarkers and potential causal factors influencing post-stroke functional outcome.

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“…Soluble cytokine receptors are typical components of body uids that modulate peripheral cytokine and lymphoid activity.It has been shown that sIL-2Rα can be produced during T lymphocyte activation as another form of IL-2Rα.It has been reported that when the expression of sIL-2R in human serum is upregulated, it acts as a "blocking factor" and can effectively bind IL-2 and play a role in inhibiting cellular immunity [36].Some studies suggest that sIL-2R is released as a decoy receptor and blocks IL-2 binding to effector T cells, [37] while others have found that sIL-2R protects IL-2 from degradation and inactivation [38].Basic studies have shown that sIL-2Rα is involved in the pathogenesis of various infectious diseases, immune-mediated diseases, neurological and cardiovascular diseases [39].For example, in laboratory analysis of Corona Virus Disease 2019 (COVID-19), sIL-2Rα was shown to be involved in the major biological processes of severe COVID-19, with both sIL-2R and IL-6 signi cantly elevated in all patients, with higher levels in critically ill patients than in severe patients and a moderate predictor of the need for hospitalization [40][41][42].A recent study suggests that measuring serum sIL-2Rα levels during the inactive phase may help identify patients with subclinical disease activity who are at risk for future active juvenile idiopathic arthritis [43].In addition, HIV + or HIV − patients with elevated sIL-2Rα levels have an increased risk of depression [44].High levels of sIL-2Rα are also genetically predicted to be associated with an increased risk of schizophrenia [45].In terms of cardiovascular disease, sIL-2Rα was positively associated with type 2 diabetes, hypertension, internal carotid artery wall thickness, CVD mortality, and stroke [39].These clinical results suggest that sIL-2Rα as an essential risk factor has a signi cant impact and predictive effect on various diseases.IL-2 and sIL2Rα are closely related, so the study of IL-2 and sIL2Rα has substantial potential in the clinical application of disease diagnosis and prognostic markers and is expected to be a biomarker indicating the outcome and prognosis of various clinical diseases.…”

Section: Discussionmentioning

confidence: 99%

Increased serum soluble interleukin-2 receptor levels in dermatomyositis are associated with Th17/Treg immune imbalance

Xie

Zhang

et al. 2023

Preprint

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Objective: In patients with dermatomyositis/polymyositis (DM/PM), especially DM patients with positive antibodies against melanoma differentiation-associated protein 5 (MDA5), the prognosis is very poor, acute progressive pulmonary interstitial disease is likely to occur, and the mortality rate is very high, while serum soluble interleukin-2 receptor (sIL-2R) is often used as a marker to assess T cell activation, it is still poorly understood. The aim of this study was to investigate the relationship between sIL-2R levels and disease activity, absolute number of peripheral blood lymphocyte subsets and related cytokines in DM patients. Method: Sixty patients with DM (32 patients with inactive DM and 28 patients with active DM) were enrolled in this study and divided into inactive and active groups according to the Myositis Disease Activity Visual Analogue Scale (MYOACT), and the absolute numbers of peripheral lymphocyte subsets and CD4 + T cell subsets were measured by flow cytometry in each group, and serum cytokine levels were measured by flow cytometry bead array. Results: Serum sIL-2R levels were positively correlated with independent visual analogue scale (VAS) in DM patients (p < 0.001), and the ratio of Th17/Treg cells was significantly higher in DM patients compared with the healthy group (P < 0.01), and there was a correlation between serum sIL-2 levels and Th17/Treg ratio. Multivariate logistic regression revealed that serum sIL-2R levels were an independent factor affecting disease activity. Serum IL-6 and IFN-γ levels were also increased in the active group compared with the inactive group (p = 0.011 and p = 0.034, respectively). In addition, receiver operating characteristic (ROC) curves showed that serum sIL-2R levels contributed to the discrimination of disease activity in DM patients, with an area under the ROC curve (AUC) of 0.757 (95% CI 0.630 – 0.884, P = 0.001). Conclusion：In DM patients, serum sIL-2R levels are not only closely related to disease activity, but also involved in their Th17/Treg immune imbalance, which is an effective indicator for evaluating DM disease activity.

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The IL-2A receptor pathway and its role in lymphocyte differentiation and function

Cited by 30 publications

References 133 publications

Proteins in the Skin and Blood in Patients with Psoriasis: A Systematic Review of Proteomic Studies

Proteins in the Skin and Blood in Patients with Psoriasis: A Systematic Review of Proteomic Studies

Causal effects of immune cell surface antigens and functional outcome after ischemic stroke: a Mendelian randomization study

Increased serum soluble interleukin-2 receptor levels in dermatomyositis are associated with Th17/Treg immune imbalance

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