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Therapeutic Challenges in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Alaa A. A. Aljabali, Murtaza M. Tambuwala, Debmalya Barh, Kenneth Lundstrom
-B*15:27, -B*46:01, -C*01:02, an-C*07:29 alleles correlate with COVID-19 susceptibility, and HLA-A*02:02, -B*15:03, and -C*12:03 may have a protective role. Genetic polymorphisms that affect ACE2 and TMPRSS2 expression also increase the risk of infection, and variations in cytokine genes such as IL6, ILR, TNF etc. could be associated with cytokine storm affecting disease severity. In the GWAS (Genome-Wide Association Study), two loci are found associated with COVID-19 severity. These are 3p21.31 harboring genes such as FYCO1, SLC6A20, CCR9, LZTFL1, XCR1, and CXCR6, and 9q34.2, where the ABO genes are located [63]. It has also been reported that people with blood group A are more susceptible to SARS-CoV-2 infections [64]. Furthermore, inborn errors of type I IFN immunity are associated with very severe COVID-19 [65].
M cells and the follicle-associated epithelium
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Hiroshi Ohno, Marian Neutra, Ifor R. Williams
M cells display distinct proteins on their basolateral membrane to attract lymphocytes into the intraepithelial pocket. For example, M cells express on their basolateral membranes a membrane-bound form of the chemokine CXCL16, a molecule that interacts with CXCR6 on T and B cells. M cells also express CD137, an integrin family member that is recognized by certain B cells. Mice deficient in CD137 have Peyer's patches, FAE, and M cells with typical apical markers, but their M cells fail to form pockets and do not harbor intraepithelial 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
In spite of being, by far, the most well-studied receptor of SDF-1α, the expression of CXCR4 in progenitor cells from BM is still controversial. Several studies demonstrated that CXCR4 expression is predominantly intracellular, while others defend the opposite (Honczarenko et al. 2006; Pelekanos et al. 2014). Pelekanos et al. compared the CXCR4 expression of both fetal BM-derived MSCs and adult cells. A very low expression (3.8% ± 0.3%) of the receptor was detected by immune staining at the cell surface of fetal MSCs; however, when permeabilized, 50% to 90% of the cells stained positive for intracellular localization of CXCR4. This pattern was also found in adult MSCs, suggesting that this phenomenon is independent of cell maturity (Pelekanos et al. 2014). On the other hand, the work of Honczarenko and colleagues reported a surface expression of around 43% of the CXCR4 receptor in adult MSCs at early passages (passage 2), as assessed by flow cytometry and further confirmed by reverse transcription polymerase chain reaction (RT-PCR). However, at later passages (12-16 passages) there was a decrease in the cell surface receptors that resulted in the lack of responsiveness to chemokines. This loss was further accompanied by the decrease of several other molecules known to be involved in the migration process, such as adhesion molecules intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) (Honczarenko et al. 2006). CXCR4 expression is dynamically regulated by external cues like hypoxia (Figure 6.3) (Schioppa et al. 2003) and can be up-regulated in adult MSCs following in vitro priming with a mixture of cytokines (Shi et al. 2007) or via viral transduction. Other cell surface molecules, such as integrin-β1, integrin-α4, and integrin ligands VCAM and ICAM, were found to be expressed by MSCs and also have a key role in the migration process and in the interaction with endothelial cells (Ip et al. 2007; Ruster et al. 2006). Although most of the current literature concerns the importance of SDF-1α and its receptor CXCR4, MSCs have been shown to express a wide number of chemokine receptors on the cell surface, which also play a role in the migration and guidance of the cells (Honczarenko et al. 2006), such as CXCR1, CXCR2, CXCR3, CXCR5, CXCR6, CX3CR1, CCR1, CCR3, CCR5, CCR7, CCR9, and CCR10 (Fox et al. 2007), although the heterogeneity of MSC populations does not allow the establishment of a specific repertoire of receptors and expression levels in culture, since they may vary with cell isolation, culture conditions, and passages (Honczarenko et al. 2006). Moreover, MSC expansion might lead to changes in MSC phenotype and to different chemokine receptors repertoire (Bara et al. 2014).
Accumulation of tissue-resident natural killer cells, innate lymphoid cells, and CD8+ T cells towards the center of human lung tumors
Published in OncoImmunology, 2023
Demi Brownlie, Andreas von Kries, Giampiero Valenzano, Nicole Wild, Emel Yilmaz, Jesper Säfholm, Mamdoh Al-Ameri, Evren Alici, Hans-Gustaf Ljunggren, Igor Schliemann, Ozan Aricak, Felix Haglund de Flon, Jakob Michaëlsson, Nicole Marquardt
Human trNK cells have been described in tumor-free lung2, however, their distribution in lung tumors is largely unexplored. Our study revealed an accumulation of trNK cells, ILCs, and CD8+ TRM cells toward the center of human lung tumors, which may, in particular for trNK cells and CD8+ TRM cells, be linked to chemokine receptors such as CXCR3 and CXCR6, which are relevant for NK cell and T cell infiltration into tumors28–30. Both CXCR3 and CXCR6 were expressed at highest frequencies on tumor center trNK cells and CD8+ TRM cells, respectively. Additionally, our data suggest that the CCL5/CCR5 axis might play a role in tumor-infiltration of CD8+ TRM cells, in line with a strong correlation between the expression of CCL5 and CD8+ T cell infiltration across different types of cancer31. In addition to varying infiltration capacities, the observed phenotype could have been induced by the tumor-microenvironment or in response to other infiltrating leukocytes. For example, circulating NK cells co-cultured with a head and neck SCC cell line and IL-15 upregulated CD49a and CD103, indicating promotion of a tissue-residency phenotype via the tumor microenvironment32. Therefore, other mechanisms leading to the accumulation of specific cell subsets such as apoptosis, metabolic differences, and lineage-dependent development must be considered.
ISG20 promotes local tumor immunity and contributes to poor survival in human glioma
Published in OncoImmunology, 2019
Mengqi Gao, Yi Lin, Xing Liu, Yiming Li, Chuanbao Zhang, Zheng Wang, Zhiliang Wang, Yulin Wang, Zongze Guo
In this study, we found that ISG20 expression is associated with many chemokines, leading to tumor infiltration of a variety of immune cells. CCL2/CCR2 is known for recruiting monocytes to the sites of inflammation produced by either tissue injury or infection, and augments the accumulation of regulatory Foxp3(+)CD4(+) T cells and of nitric oxide- and YM-1-expressing macrophages and microglia.52 CCL5 induces chemotaxis in T cells and monocytes.53–56 CCL23 might play vital roles in inflammation through the recruitment of macrophages and dendritic cells.57 CCRL2/CXCR2 is the main neutrophil attractor in vitro,58 and is involved in the control of both innate and adaptive immune responses.59 CXCR6, a chemokine receptor for CXCL16 that is expressed on a subset of CD4 + T helper 1 cells and natural killer T cells, is involved in lymphocyte homing and modulates the development and progression of atherosclerosis.60 Collectively, elevated expression of these chemokines may contribute to glioma progression by recruiting macrophages and neutrophils to the local tumor environment. Nevertheless, we did not find a significant association of microglia with ISG20 expression, suggesting that the ISG20-associated macrophages were monocyte-derived instead of residual microglial cells.61
Chemokines as the critical factors during bladder cancer progression: an overview
Published in International Reviews of Immunology, 2021
Amir Sadra Zangouei, Amir Abbas Hamidi, Hamid Reza Rahimi, Ehsan Saburi, Majid Mojarrad, Meysam Moghbeli
CMTM is belonged to the MARVEL domain containing protein family involved in reproduction, immune response, tumorigenesis, and apoptosis induction. It acts as a tumor suppressor gene in different types of cancer, and also regulates the tumor cell migration [89]. CMTM8 is believed to suppress the EGFR signaling pathway, which is up regulated in various malignant tumors [170]. In other tumor types, CMTM8 induced tumor cell apoptosis. Moreover, CMTM8 down regulation by c-MET results in EMT [171]. Levels of CMTM8 protein expression were assessed in BCa patients that showed its down regulation was significantly correlated with advanced tumor grade and stage. CMTM8 ectopic expression also reduced cell viability, migration, and colony formation in BCa cell line [88]. CMTM8 up regulation suppressed the cell proliferation and migration, while induced apoptosis in BCa. There was also significant association between CMTM8 expression, invasion, and patient survival. Moreover, CMTM8 was significantly over expressed in low-grade BCa cell line (RT4) and under expressed in high-grade BCa cell line (T24). The CMTM8 over expression reduced cell proliferation and migration through EGF and SDF1 in T24 cells. CMTM8 down regulation was observed in high grade in comparison with low grade BCa tissues. Decreased CMTM8 expression was associated with poor survival among BCa patients [89]. CXCL16 is a chemokine produced by immune cells, fibroblasts, keratinocytes, and tumor cells [135]. CXCR6 is upregulated following T cells activation. It is also expressed on CD4 + T cells, NK cells, DCs, and innate lymphoid cells [172]. There were higher and lower expressions of CXCR6 and CXCL16 respectively in BCa tissues compared with controls. The CXCL16/CXCR6 expressions were correlated with patients survival. CXCL16 was also associated with lymphovascular invasion. Moreover, there were significant correlations between CXCR6 expression, T stage, and perineural invasion. They concluded that the CXCL16/CXCR6 expression was associated with tumor aggressiveness [90].