Direct effects of interleukin-8 on growth and functional activity of T lymphocytes

Meniailo, Maksim Evgenievich; Малащенко, В. В.; Shmarov, V.A.; Газатова, Н. Д.; Melashchenko, Olga Borisovna; Гончаров, А. Г.; Селедцова, Г. В.; Селедцов, В. И.

doi:10.1016/j.intimp.2017.06.023

Cited by 19 publications

(16 citation statements)

References 21 publications

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“…This suggests that the inflammatory context created by these cytokines that leads to T cell activation is not enough to generate an adequate anti-viral response without the proper recruitment signals to attract activated T cells. CCL4 signals through the receptor CCR5 to attract T cells to the site of inflammation and depending on the immune context, this molecule recruits differently activated T cells ( 37 , 38 ). Moreover, it was recently shown, by single cell analysis, down regulation of CCL4 expression in peripheral myeloid cell compartments in patients with Mild and Severe COVID-19 ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

et al. 2021

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Expression of CCR5 and its cognate ligands have been implicated in COVID-19 pathogenesis, consequently therapeutics directed against CCR5 are being investigated. Here, we explored the role of CCR5 and its ligands across the immunologic spectrum of COVID-19. We used a bioinformatics approach to predict and model the immunologic phases of COVID so that effective treatment strategies can be devised and monitored. We investigated 224 individuals including healthy controls and patients spanning the COVID-19 disease continuum. We assessed the plasma and isolated peripheral blood mononuclear cells (PBMCs) from 29 healthy controls, 26 Mild-Moderate COVID-19 individuals, 48 Severe COVID-19 individuals, and 121 individuals with post-acute sequelae of COVID-19 (PASC) symptoms. Immune subset profiling and a 14-plex cytokine panel were run on all patients from each group. B-cells were significantly elevated compared to healthy control individuals (P<0.001) as was the CD14+, CD16+, CCR5+ monocytic subset (P<0.001). CD4 and CD8 positive T-cells expressing PD-1 as well as T-regulatory cells were significantly lower than healthy controls (P<0.001 and P=0.01 respectively). CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, and VEGF were all significantly elevated compared to healthy controls (all P<0.001). Conversely GM-CSF and CCL4 were in significantly lower levels than healthy controls (P=0.01). Data were further analyzed and the classes were balanced using SMOTE. With a balanced working dataset, we constructed 3 random forest classifiers: a multi-class predictor, a Severe disease group binary classifier and a PASC binary classifier. Models were also analyzed for feature importance to identify relevant cytokines to generate a disease score. Multi-class models generated a score specific for the PASC patients and defined as S1 = (IFN-γ + IL-2)/CCL4-MIP-1β. Second, a score for the Severe COVID-19 patients was defined as S2 = (IL-6+sCD40L/1000 + VEGF/10 + 10*IL-10)/(IL-2 + IL-8). Severe COVID-19 patients are characterized by excessive inflammation and dysregulated T cell activation, recruitment, and counteracting activities. While PASC patients are characterized by a profile able to induce the activation of effector T cells with pro-inflammatory properties and the capacity of generating an effective immune response to eliminate the virus but without the proper recruitment signals to attract activated T cells.

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Section: Discussionmentioning

confidence: 99%

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

et al. 2021

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“…Higher levels of IL-8 have been reported sarcoidosis BALF 45 and serum, with the latter correlating with pulmonary 46 and chronic disease 47 . IL-8 signaling has recently been reported to directly regulate adaptive T cell reactivity 48 and phagosome function. Thus, our findings are not surprising but suggest that future studies investigating IL-8 signaling could improve the understanding of sarcoidosis pathogenesis and potentially phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Novel protein pathways in development and progression of pulmonary sarcoidosis

Bhargava

Viken

Barkes

et al. 2020

Sci Rep

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Pulmonary involvement occurs in up to 95% of sarcoidosis cases. In this pilot study, we examine lung compartment-specific protein expression to identify pathways linked to development and progression of pulmonary sarcoidosis. We characterized bronchoalveolar lavage (BAL) cells and fluid (BALF) proteins in recently diagnosed sarcoidosis cases. We identified 4,306 proteins in BAL cells, of which 272 proteins were differentially expressed in sarcoidosis compared to controls. These proteins map to novel pathways such as integrin-linked kinase and IL-8 signaling and previously implicated pathways in sarcoidosis, including phagosome maturation, clathrin-mediated endocytic signaling and redox balance. In the BALF, the differentially expressed proteins map to several pathways identified in the BAL cells. The differentially expressed BALF proteins also map to aryl hydrocarbon signaling, communication between innate and adaptive immune response, integrin, PTEN and phospholipase C signaling, serotonin and tryptophan metabolism, autophagy, and B cell receptor signaling. Additional pathways that were different between progressive and non-progressive sarcoidosis in the BALF included CD28 signaling and PFKFB4 signaling. Our studies demonstrate the power of contemporary proteomics to reveal novel mechanisms operational in sarcoidosis. Application of our workflows in well-phenotyped large cohorts maybe beneficial to identify biomarkers for diagnosis and prognosis and therapeutically tenable molecular mechanisms.

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“…The receptors CXCR1 and CXCR3 play essential functions during the immune response against TB [30]. Although these receptors are preferentially expressed in neutrophils from TB patients, some reports showed that CXCR1 and CXCR2 could also be expressed on the cell surface of effector CD4+ and CD8+ T cells [31,32]. Here, we addressed possible differences in the expression of CXCR1 and CXCR3 in CD4+ and CD8+ T cells from DS-TB and MDR-TB patients (Figures 6 and 7, respectively).…”

Section: Cxcr1+cxcr3+ T Cells Are Increased During Mdr-tbmentioning

confidence: 96%

Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity

Ocaña-Guzmán

Téllez-Navarrete

Ramón‐Luing

et al. 2021

Journal of Immunology Research

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy.

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Direct effects of interleukin-8 on growth and functional activity of T lymphocytes

Cited by 19 publications

References 21 publications

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

Novel protein pathways in development and progression of pulmonary sarcoidosis

Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity

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