M cells and the follicle-associated epithelium
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
FAE cells differ from villus cells in their ability to release certain chemokines that attract immune cells toward the FAE and thus to sites of organized lymphoid tissue. In the small intestine of mice and humans, for example, chemokine CCL20, also designated macrophage inflammatory protein-3α (MIP-3α), is constitutively expressed in the FAE but not in the villus epithelium (Figure 15.2). CCL20 attracts subpopulations of DCs and lymphocytes that express the chemokine receptor CCR6. Mice that lack CCR6 have lower numbers of CD11c+ DCs in the subepithelial dome regions of Peyer's patches and have an impaired humoral immune response to orally administered antigen and certain enteropathogenic viruses. Cells of the mouse FAE also express CCL9 (analogous to CCL23 in humans), which attracts CCR1-expressing myeloid DCs, and CXCL16, which attracts CXCR6-expressing B and T lymphocytes into Peyer's patches.
Palmoplantar psoriasis
M. Alan Menter, Caitriona Ryan in Psoriasis, 2017
The relationship between tonsillitis and PPP onset or its worsening is not entirely clear. Japanese studies have found varying degrees of therapeutic success, ranging from 16.7% to over 75% improvement for PPP patients following tonsillectomy.37,38 A randomized controlled trial on the effect of tonsillectomy in PPP patients showed that 86% of patients who underwent a tonsillectomy had a sustained response with significant reduction in the Palmoplantar Psoriasis Area and Severity Index (PPPASI) score, ranging from 30% to 90% reduction. Nevertheless, some patients experienced psoriasis relapse after initial improvement.39 Histologically, the tonsils of PPP patients show significantly increased numbers of lymphoid follicles surrounded by reticular crypt epithelial cells compared with controls. IL-6 concentrations were higher in PPP patients’ tonsils than in controls.40 IL-6 has also been found significantly elevated in PPP serum. Furthermore, after tonsillectomy there was a significant reduction in the serum concentration of IL-6 that paralleled a PPP improvement.41 In vitro stimulation with streptococcal antigens on PPP tonsillar and peripheral blood T cells showed a significant upregulation of IL-6, IFN-γ, TNF-α, and CCR6.42–44 CCL20, CCR6 ligand, mediates recruitment of lymphocytes and is overexpressed in PPP lesions. Tonsillectomy of PPP patients resulted in a decreased CCR6 expression on blood T cells.44
Cell Recruitment for Intervertebral Disc
Raquel M. Gonçalves, Mário Adolfo Barbosa in Gene and Cell Delivery for Intervertebral Disc Degeneration, 2018
CCL20 expression in NP cells has also been reported. Both CCL20 and its receptor CCR6 have been associated with IVD degenerative conditions (Zhang et al. 2013b). CCR6, the only receptor of CCL20, is specifically expressed on the Th17 cell surface and is related to the recruitment of these cells in several inflammatory diseases; higher levels of IL-17 (T-helper 17 and Th17 associated cytokine) have been observed in patients with IVD degeneration (Shamji et al. 2010). This interaction was reinforced in a study using a rat model; Zhang et al. (2016) could show a positive correlation between the expression levels of CCL20-, CCR6-, and IL-17-producing cells, suggesting that the recruitment of these cells to degenerated IVD tissues occurred via the CCL20/CCR6 system in vivo. An association between AF cell migration and CXCL10 had already been established, suggesting a role of this chemokine in AF homeostasis and repair (Hegewald et al. 2012). Taken together, these results demonstrate the involvement of several chemotactic molecules in the disc degeneration pathogenesis. Moreover, most of the studies could identify cytokines and chemokines that are directly or indirectly related to the recruitment of immune cells, thereby intensifying the inflammatory response and the release of neurotrophines, promoting pain. The study of these molecules is relevant not only for the design of new therapies, by targeting symptomatic discs and the associated inflammation, but also for understanding the players in stem cell recruitment for repair.
Mechanical strain mimicking breathing amplifies alterations in gene expression induced by SiO2 NPs in lung epithelial cells
Published in Nanotoxicology, 2019
Carmen Schmitz, Jennifer Welck, Isabella Tavernaro, Marianna Grinberg, Jörg Rahnenführer, Alexandra K. Kiemer, Christoph van Thriel, Jan G. Hengstler, Annette Kraegeloh
In this study, for the first time, the effects of silica NPs on gene expression of mechanically stretched lung epithelial cells were analyzed. Only under the combined conditions, upregulation of nine genes related to proinflammatory responses (Table 4) was induced. According to the gene array data, the chemokine CCL20 was among the strongest upregulated genes. CCL20 is known to recruit immature dendritic cells and subpopulations of T-lymphocytes and B cells (Schutyser et al. 2003). CXCL8, encoding for the neutrophil attracting chemokine IL-8, was also markedly upregulated (Table 4). In comparison, no increase in the secretion of IL-8 by stretched and silica NPs treated primary endothelial cells (HUVEC) was found by Freese et al. (2014). In addition, in this study, a moderate (2-4-fold) upregulation was observed for CCL2, CXCL1, CXCL2, CXCL3, IL6, ICAM1, and PTX3. An augmented expression of ICAM-1 induced by silica NPs combined with mechanical strain was also found in endothelial cells (Huh et al. 2010). In the same study, 12 nm colloidal silica NPs were shown to increase ROS generation when applied to stretched alveolar epithelial cells.
Emerging therapeutic targets for nasopharyngeal carcinoma: opportunities and challenges
Published in Expert Opinion on Therapeutic Targets, 2020
Valentin Baloche, François-Régis Ferrand, Anna Makowska, Caroline Even, Udo Kontny, Pierre Busson
In the section about NPC tumor microenvironment, we have mentioned several biomolecules released by malignant cells which are suspected to contribute to the local immunosuppression, including LIF, CCL20 and galectin-9. Antibodies neutralizing LIF are currently in clinical development for human malignancies but, to our knowledge, have not been specifically tested in NPC patients [115](NCT03490669). The development of antibodies neutralizing CCL20 is much less advanced [116]. Therapeutic antibodies neutralizing extra-cellular galectin-9 are currently under pre-clinical development [117]. CCR4 is a chemokine receptor expressed at the surface of T-regs which mediates the chemotactic effect of CCL17 and CCL22. Both cytokines are abundant in some EBV-related malignancies like NK/T cell lymphomas [118]. It would be interesting to know their status in NPCs. Small molecules blocking CCR4 are currently in pre-clinical development (American Association for Cancer Research meeting, 2018, abstract #4752).
The use of biomarkers as a tool for novel psoriatic disease drug discovery
Published in Expert Opinion on Drug Discovery, 2018
Dinesh Aggarwal, Nikita Arumalla, Hannah Jethwa, Sonya Abraham
CCL20 is a recognized chemokine ligand, attracting immune cells, including Th17 and DCs, to sites of inflammation. Harper et al. demonstrated upregulation of CCL20 and CC chemokine receptor (CCR6) in both human KCs and mice models by IL-17 and TNF-α, thereby creating a positive feedback mechanism to maintain Th17 cell and DC presence in inflamed sites [89]. The monoclonal antibody, GSK3050002, targets CCL20 and prevents its binding to CCR6, thus inhibiting recruitment of immune cells to synovium and skin. Phase I trials are in progress to evaluate its mechanism of action, safety, and efficacy in psoriatic disease, representing a novel class of biomarker target [90].