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Immuno-Pathologic Basis of COVID-19 and the Management of Mild and Moderate Cases
Published in Srijan Goswami, Chiranjeeb Dey, COVID-19 and SARS-CoV-2, 2022
Debdeep Dasgupta, Srijan Goswami, Chiranjeeb Dey
Activation of non-resident macrophages of the lungs (monocyte-derived macrophages) and increased secretion of IL-1β are characteristic features of SARS-CoV-2 infection. These events together are responsible for severe damage (tissue injury, endothelial damage, and ARDS) associated with cytokine storms. The damage to pulmonary microvasculature and respiratory membranes (see Chapter 3) is caused by abnormally elevated levels of IL-6, IL-8, IL-1β, tumor necrosis factor-α. GM-CSF, CCL2, CCL3. CCL5, CXCL8, CXCL9, CXCL10, and reactive oxygen species (ROS) lead to vascular leakage, alveolar edema, hypoxia, pulmonary fibrosis, and death. In severe COVID-19 patients, blood analysis revealed abnormally increased levels of interferon-γ, IL-1, IL-6, IL-12, and transforming growth factor-β, IL-8, CCL2, CXCL-9, and CXCL10 (Price et al., 2020; Dutta et al., 2020; Fajgenbaum and June, 2020) (Figure 7.4).
Anti-infectious innate and adaptive immune responses
Published in Gabriel Virella, Medical Immunology, 2019
Carl Atkinson, Gabriel Virella
CC Chemokines include four major cytokines, which act predominantly on mononuclear cells, the cells that predominantly express the receptors for this group of cytokines: CCL5 (RANTES, regulated on activation, normal T-cell expressed and secreted) is released by T cells and attracts T cells with memory phenotype, NK cells, eosinophils, and mast cells.Macrophage inflammatory proteins (MIPs) are released by monocytes and macrophages and attract eosinophils, lymphocytes, and NK and LAK cells.Macrophage chemotactic proteins (MCPs) are produced by monocytes, macrophages, and related cells and attract monocytes, eosinophils, NK, and LAK cells.Eotaxin is a chemokine induced by IL-4 that recruits eosinophils and Th2 CD4+ T cells to the sites of allergic inflammation.β-Defensins are released primarily by granulocytes and have also been characterized as chemotactic for T lymphocytes.
Cell Recruitment for Intervertebral Disc
Published in Raquel M. Gonçalves, Mário Adolfo Barbosa, Gene and Cell Delivery for Intervertebral Disc Degeneration, 2018
Catarina Leite Pereira, Sibylle Grad, Mário Adolfo Barbosa, Raquel M. Gonçalves
A summary of cytokines and chemokines identified to date that are expressed during disc degeneration is presented in Table 6.2. Among several factors, CCL5/RANTES has been identified by Pattappa et al. (2014) together with CXCL6, in the conditioned media of degenerated IVD organ cultures using proteomic analysis. In migration assays, the CCL5 and CCL5/CXCL6 immunoprecipicitation resulted in a reduced MSC migration toward conditioned medium, while the CXCL6 immunoprecipicitation did not affect MSC chemotaxis. In addition, mRNA expression analysis of MSCs cultured in IVD degenerative media revealed a significant increase in the expression of the CCL5 receptors, CCR1 and CCR4. CCL5/RANTES expression in the tissue of both bovine and human discs was further confirmed by immunohistochemistry (Pattappa et al. 2014).
The discovery and development of oncolytic viruses: are they the future of cancer immunotherapy?
Published in Expert Opinion on Drug Discovery, 2021
Shunchuan Zhang, Samuel D Rabkin
Chemokines are a family of secreted chemoattractant proteins that mediate immune cell trafficking to influence immune responses, both beneficially and detrimentally, promoting tumorigenesis and/or immunosuppression [106]. OVs have been armed with various chemokines (Table 2). CCL5 (RANTES) is a proinflammatory chemokine recruiting T cells, DCs, macrophages, and NK cells to the TME [106]. An oAd expressing RANTES increased tumors-specific TILs and NK cells and inhibited primary and distal tumors [107]. CCL5 expressing oVV (vvCCL5) had decreased pathogenicity, increased immune cell infiltration (effector CD4 + T cells and DCs), virus in the tumor, and inhibition of tumor growth [108]. vvDD-CCL19 treatment of mouse tumors also resulted in increased DC and effector T cell infiltration and inhibition of tumor growth [109]. In contrast, intravenous injection of oVV expressing CXCL11 (vvDD-CXCL11) was no better than parental vvDD in a subcutaneous model, despite increasing TILs [110], while it greatly extended survival in an intraperitoneal tumor model [111]. OVSV expressing CXCL9 did not increase TILs nor improve inhibition of tumor growth in mouse syngeneic tumors [112].
Molecular profiling of primary uveal melanomas with tumor-infiltrating lymphocytes
Published in OncoImmunology, 2019
Pierre L Triozzi, Lynn Schoenfield, Thomas Plesec, Yogen Saunthararajah, Raymond R Tubbs, Arun D Singh
The cellular source of the immune factors identified and the functional activities of TILs within uveal melanomas merit further study. There is increasing interest in characterizing TILs as biomarkers in cancer immunotherapy as well as targets for immune manipulation. TILs are further undergoing evaluation as a source of cells for adoptive immunotherapy.54 Recent clinical cancer immunotherapy trials have included pre-treatment tumor gene expression profiling, and clinical benefit has been shown to correlate with a gene signature that included T-cell and chemokine markers. High expression of CCL5, CXCL9, and CXCL10 were found to be associated with a favorable clinical outcome in patients with cutaneous melanoma administered a melanoma vaccine.55 Thus, characterization of TILs could lead to an improvement in the clinical efficacy of cancer immunotherapy, by permitting the selection of patients most likely to have a beneficial response. Further investigations of TILs may also help identify the main factors that make immune modulation ineffective and suggest specific manipulations. For example, CD8+ Tregs are potentially modifiable by blockade of LAG-3 interactions and a blocking LAG-3 immunoglobulin fusion protein is currently being evaluated in clinical trials.56 Chemokine inhibitors, such as a CCL5 antagonist, may be potent immune-modifying agents with potential therapeutic benefit and are also under development.57
Analysis of Inflammatory Gene Expression Profile of Peripheral Blood Leukocytes in Type 2 Diabetes
Published in Immunological Investigations, 2019
Humera Inayat, M. Kamran Azim, Akhter Ali Baloch
We also found up-regulation of CCL5 and CCR5 transcripts in NT-T2DM patients. CCL5 (C-C motif ligand 5) also called as RANTES (regulated-on-activation-normal-T-cell-expressed-and-secreted) belongs to the C-C chemokine group. Previous studies have shown the association between CCL5 and its receptor CCR5, and T2DM, glucose intolerance and obesity (Herder et al., 2008; Xu et al., 2015; Yao et al., 2014). However, the mechanism of their actions in insulin resistance and glucose metabolism remains debatable. Kitade et al. (2012) reported that knockdown of CCR5 gene protected mice from obesity-mediated inflammation, recruitment of macrophage and insulin resistance. In contrast, Kennedy et al. (2013) reported that CCR5 knockdown impairs glucose tolerance and insulin signaling in adipose tissues and muscles. We found that expression of CCL5 and CCR5 transcripts was elevated in circulatory leukocytes of the NT-T2DM patients. This finding correlates with previous reports which demonstrated that serum CCL5 levels are increased in T2DM (Dworacka et al., 2014). However, the Met-T2DM group showed statistically significant down-regulation of both CCL5 and CCR5 compared to NT-T2DM and INS-T2DM groups which is another indication of metformin’s anti-inflammatory activity.