Innate and Adaptive Immune Dysfunction and Necrotizing Enterocolitis
David J. Hackam in Necrotizing Enterocolitis, 2021
Macrophages are mature in terms of numbers and function by midgestation; however, while adult intestinal macrophages exhibit inflammatory anergy and do not secrete cytokines to induce a local inflammatory response, it has been shown that fetal macrophages do express inflammatory cytokines at levels that developmentally decrease toward term (55). TGFβ2 suppresses this inflammatory cytokine production (55). The migration of macrophages to the site of intestinal injury is regulated by the chemokine CXCL5 found in the epithelial and muscular layers of the intestine, which attracts myeloid cells and is also elevated in immature intestinal tissue (56). In contrast, neutrophils have limited chemotactic ability until post-term (57). Thus, intestinal inflammatory infiltrates in preterm infants have a macrophage predominance.
Epidemiology and Pathogenesis of COVID-19
Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga in The Covid-19 Pandemic, 2023
Other cells released in the event of a viral infection include inflammatory cytokines; TNF-α, IL-6, 2, and 10, IFN-α/-γ, Granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein 3 (MCP3), macrophage inflammatory protein 1-α (MIP 1 α), which have shown enhanced levels after infection with a coronavirus leading to the migration of inflammatory cells in the lungs resulting in ARDS which has a high mortality rate especially in critical patients. Along with cytokines, increased levels of chemokines such as CCL2/MCP1, interferon gamma-induced protein 10 (IP-10), CXCL1 as well as CXCL5 have also been observed. One study carried out a transcriptomic analysis on infected peripheral blood mononuclear cells (PBMCs) and infected cells from the patient’s bronchoal-veolar lavage fluid (BALF) to ascertain host responses. The results showed an upregulation of inflammatory cytokines such as CCL2, CXCL2, CCL8, CXCL1, IL33, CCL3L1 in the BALF and CXCL10, TNFSF10, TIMP1, C5, IL18, AREG, NRG1, IL10 in the PBMCs which led to a cytokine storm in patients causing severe inflammation in the lungs. Moreover, further analysis also revealed activated apoptotic and P53 signaling pathways that could be the reason behind the lymphopenia seen in many severely ill COVID-19 patients [12].
Inflammation, Stem Cell Therapy, and Cardiac Repair
Shyam S. Bansal in Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Mesenchymal stem cells produce a paracrine secretome that can directly modulate the recruitment, retention, and viability of neutrophil populations. MSC secretome is enriched in chemotactic signaling molecules CXCL1, CXCL2, CXCL5, and CXCL8 – all of which elicit neutrophil recruitment.27 Additionally, MSC-mediated production of IL-6 has been shown to directly affect neutrophil viability in co-culture systems.28 Exposure of neutrophils to MSC cultures that are deficient in IL-6 compromises neutrophil viability.29 Understanding how stem cells mediate the viability, recruitment, and phenotype of neutrophil populations in the infarcted heart can provide insight into how cell-based therapies can modulate the clearance of necrotic myocardium, cardiac rupture, and establishment of a pro-reparative state that promotes myocardial wound healing.
Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice
Published in Pharmaceutical Biology, 2023
Zhe Liu, Jin-ru Zhang, Yong-xiang Huang, Xue-ying Li, Hai-peng Zhu, Rui-yi Yang, Song Chen
Ulcerative colitis pathogenesis has not been fully elucidated. DSS-induced colitis mouse models are most often used to recapitulate UC in humans and have become indispensable tools for elucidating the pathogenesis and potential therapeutic targets for UC (Eichele and Kharbanda 2017). In this study, the transcriptomic analysis indicated the decreased transcription of the HSP family members and Nr1d1 in DSS-treated mice. Several studies have reported the protective roles of HSP70 (with isoforms Hspa1a and Hspa1b), HSP40 (Dnajb1), and HSP110 (Hsph1) in DSS-induced colitis (Ohkawara et al. 2006; Tanaka et al. 2007; Berthenet et al. 2016). Nr1d1 is an important circadian pathway regulatory gene associated with DSS-induced colitis (Chen et al. 2022). We also identified several upregulated genes, such as chloride channel accessory 4B (Clca4b), Nos2, Prss22/Prss27, and Cxcl5 (ENA78), as well as an upregulated KEGG pathway, namely, IL-17 signalling. The critical role of IL-17 signalling in colitis has previously been documented (Zhang et al. 2006; Ito et al. 2008). CXCL5, a chemokine that is preferentially expressed in the intestinal epithelium of UC patients, mediates neutrophil recruitment (Z'Graggen et al. 1997). Our results suggest that these key molecules are potential therapeutic targets in UC.
Leukemia cell-derived microvesicles induce T cell exhaustion via miRNA delivery
Published in OncoImmunology, 2018
Jieke Cui, Qing Li, Mei Luo, Zhaodong Zhong, Shu Zhou, Lin Jiang, Na Shen, Zhe Geng, Hui Cheng, Li Meng, Shujuan Yi, Hui Sun, Feifei Wu, Zunmin Zhu, Ping Zou, Yong You, An-Yuan Guo, Xiaojian Zhu
We speculate MV might participate in T cell exhaustion and checkpoints via NF-κB pathway regulation (Fig. 7J). NF-κB is one of the most important functional associated pathways but also regulates the expression of PD-119 and is crucial for regulation of T-cell immune checkpoint inhibitors in cancer.20 IL-1β is an upstream activator of NF-κB.21 High levels of miR-21-5p from MVs can down-regulate IL-1β to reduce NF-κB activity from the upstream signal. CXCL5 is a downstream effector of NF-κB, which could accelerate cell proliferation and migration.18 We consider that miR-92 a-3p, miR-21-5p and miR-16-5p reduce the level of CXCL5 after MV incubation. SerpinB2, serves as a negative feedback mechanism to avoid active-induced apoptosis and dysfunction,22 was also down-regulate and might contribute to the T cell exhaustion.
CXCL5-mediated accumulation of mature neutrophils in lung cancer tissues impairs the differentiation program of anticancer CD8 T cells and limits the efficacy of checkpoint inhibitors
Published in OncoImmunology, 2022
Francesca Simoncello, Giulia Maria Piperno, Nicoletta Caronni, Roberto Amadio, Ambra Cappelletto, Giulia Canarutto, Silvano Piazza, Silvio Bicciato, Federica Benvenuti
Infiltration by neu is often caused by oncogene-driven overexpression of chemokines.30 Overexpression of CXCL5 that binds CXCR2 drives neutrophils infiltration in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC),31,32 melanoma33,34 bladder cancer,35 prostate cancer31 and breast cancer.36,37 In lung tissues, seminal studies described CXCL5 as critical to recruit neutrophils during inflammation and infection.38–40 In lung cancer, CXCL5 was shown to induce cancer cell proliferation, migration,41,42 autophagy43 and epithelial mesenchymal transition44 and it is associated with poor prognosis.45,46 CXCL5 is also expressed in experimental models of lung cancer,47,48 however the direct link to neutrophils recruitment and interference with anti-tumoral T cell responses has not been demonstrated.
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