Pulmonary Guardians and Special Regulatory Devices in the Lung of Nile Monitor Lizard (Varanus niloticus) with Special Attention to the Communication Between Telocyte, Pericyte, and Immune Cells

2021 ◽  
pp. 1-7
Author(s):  
Dalia Mohamedien ◽  
Mahmoud Awad

Monitor lizards are acclimatized to a variety of environments. Most of the monitor species are terrestrial, although there are arboreal and semiaquatic monitors. Such accommodation requires unique cellular structure and regulatory devices in various organs, particularly their lungs. This study aimed to report the pulmonary guardians and special regulatory devices that may guard and promote the function of the lungs of the Nile monitor lizards (Varanus niloticus). Specially structured vessels were recorded in the pulmonary tissue involving atypical glomus vessels, vessels with variable wall thickness, and a venule with specialized internal elastic membrane. Moreover, numerous lung resident guardians could be identified including both alveolar and interstitial macrophages, dendritic cells, mast cells, and B- and T-lymphocytes. Pericytes were demonstrated surrounding the capillary endothelium with a characteristic direct hetero-cellular junction with telocytes. Telocytes established a microenvironment through an indirect hetero-cellular junction with the interstitial macrophage, dendritic cells, and pneumocyte type II. Collectively, these data indicate a significant role played by the specially structured vessels and the resident immune cells in guarding the pulmonary tissue of the Nile monitor lizards and promoting its function. Telocytes are suggested to play a key role in angiogenesis and cellular communication to promote the function of the immune cells.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gen Zou ◽  
Jianzhang Wang ◽  
Xinxin Xu ◽  
Ping Xu ◽  
Libo Zhu ◽  
...  

Abstract Background Endometriosis is a refractory and recurrent disease and it affects nearly 10% of reproductive-aged women and 40% of infertile patients. The commonly accepted theory for endometriosis is retrograde menstruation where endometrial tissues invade into peritoneal cavity and fail to be cleared due to immune dysfunction. Therefore, the comprehensive understanding of immunologic microenvironment of peritoneal cavity deserves further investigation for the previous studies mainly focus on one or several immune cells. Results High-quality transcriptomes were from peritoneal fluid samples of patients with endometriosis and control, and firstly subjected to 10 × genomics single-cell RNA-sequencing. We acquired the single-cell transcriptomes of 10,280 cells from endometriosis sample and 7250 cells from control sample with an average of approximately 63,000 reads per cell. A comprehensive map of overall cells in peritoneal fluid was first exhibited. We unveiled the heterogeneity of immune cells and discovered new cell subtypes including T cell receptor positive (TCR+) macrophages, proliferating macrophages and natural killer dendritic cells in peritoneal fluid, which was further verified by double immunofluorescence staining and flow cytometry. Pseudo-time analysis showed that the response of macrophages to the menstrual debris might follow the certain differentiation trajectory after endometrial tissues invaded into the peritoneal cavity, that is, from antigen presentation to pro-inflammation, then to chemotaxis and phagocytosis. Our analyses also mirrored the dysfunctions of immune cells including decreased phagocytosis and cytotoxic activity and elevated pro-inflammatory and chemotactic effects in endometriosis. Conclusion TCR+ macrophages, proliferating macrophages and natural killer dendritic cells are firstly reported in human peritoneal fluid. Our results also revealed that immune dysfunction happens in peritoneal fluid of endometriosis, which may be responsible for the residues of invaded menstrual debris. It provided a large-scale and high-dimensional characterization of peritoneal microenvironment and offered a useful resource for future development of immunotherapy.


2019 ◽  
Author(s):  
Maik Negendank ◽  
Vidal Sanabria ◽  
Sören Müller ◽  
W. Reimers

2021 ◽  
Vol 22 (13) ◽  
pp. 6878
Author(s):  
Yaser Hosny Ali Elewa ◽  
Mahmoud Mansour Abd Elwakil ◽  
Osamu Ichii ◽  
Teppei Nakamura ◽  
Sherif Kh. A. Mohamed ◽  
...  

Recently, we clarified the function of mediastinal fat-associated lymphoid clusters (MFALCs) in the progression of several respiratory diseases. However, their role has not yet been identified in the lung asthmatic condition. Hence, we compared the immune cells in lung and MFALCs of C57BL/6N mice on days 3 and 7 following intranasal instillation of either papain (papain group “PG”) or phosphate buffer saline (PBS) (vehicle group “VG”). The PG showed significantly prominent MFALCs, numerous goblet cells (GCs), and higher index ratios of different immune cells (macrophages, natural helper cells (NHC), B- and T-lymphocytes) within the MFALCs and lung than in the VG on both days 3 and 7. Interestingly, a tendency of decreased size of MFALCs and a significant reduction in the number of GCs and immune cells were observed within the MFALCs and lung in the PG on day 7 than on day 3. Furthermore, the quantitative parameters of these immune cells in MFALCs were significantly and positively correlated with the size of MFALCs and immune cells in the lung. This suggested that the possible crosstalk between immune cells within MFALCs and the lung could play a critical role in the progression and recovery of the acute inflammatory lung asthma.


Blood ◽  
2009 ◽  
Vol 113 (1) ◽  
pp. 46-57 ◽  
Author(s):  
Bin Zhang ◽  
Rui Liu ◽  
Dan Shi ◽  
Xingxia Liu ◽  
Yuan Chen ◽  
...  

Abstract Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2–dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 456 ◽  
Author(s):  
Philippe Saas ◽  
Alexis Varin ◽  
Sylvain Perruche ◽  
Adam Ceroi

There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC). The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists) in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.


Acta Naturae ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 68-76
Author(s):  
G. V. Kornilaeva ◽  
A. E. Siniavin ◽  
A. Schultz ◽  
A. Germann ◽  
C. Moog ◽  
...  

The anti-HIV activity of a new humic substance-derived preparation has been studied in individual pools of immune cells (CD4+ T lymphocytes, macrophages, dendritic cells). Near-complete inhibition of the HIV infection (by more than 90%) was achieved by treating each of the abovementioned cell types with non-toxic concentrations of the preparation. The inhibitory effect demonstrates the possibility of preventing the depletion of a significant portion of functionally important immune cells. A comparative study of infection inhibition in individual cell pools has allowed us to reveal the differences in the preparations effectiveness in each of the cell populations. A R5-tropic HIV-1 infection in macrophages exhibited maximum sensitivity to the preparation: 90% and 50% inhibition of the infection were observed in the presence of concentrations as low as 1.4 and 0.35 g/ml, respectively. A 15- and 19-fold higher concentration was required to achieve the same extent of inhibition in dendritic cells infected with the same strain. The effectiveness of the drug in CD4 + T lymphocytes is quite comparable to its effectiveness in macrophages. The drug is universally effective for both the T- and M-tropic variants of HIV-1.


2021 ◽  
Author(s):  
Yanling Ma ◽  
WenBo Qi ◽  
BaoHong Gu ◽  
XueMei Li ◽  
ZhenYu Yin ◽  
...  

Abstract Objective: To investigate the association between ILDR1 and prognosis and immune infiltration in gastric cancer. Methods: We analyzed the RNA sequencing data of 9736 tumor tissues and 8587 normal tissues in the TCGA and GTEx databases through the GEPIA2 platform. The expression of ILDR1 in gastric cancer and normal gastric mucosa tissues with GEPIA and TIMER. Clinical subgroup analysis was made through Kaplan-Meier analysis. Analyzed the correlation between ILDR1 and VEGFA expression in gastric cancer, through the gene sequencing data of gastric cancer in TCGA. Explored the relationship between ILDR1 methylation and the prognosis of gastric cancer patients through the MethSurv database. The correlation between ILDR1 and immune cells and the correlation of copy number variation were explored through the TIMER database. Results: ILDR1-high GC patients had a lower PFS and OS. High ILDR1 expression was significantly correlated with tumor grade. There was a negative correlation between the ILDR1 expression and the abundances of CD8+ T, Macrophages and DC and etc. The methylation level of ILDR1 is associated with a good prognosis of gastric cancer. ILDR1 copy number variation was correlated with immune cells, IDLR1 arm-loss was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, and arm-duplication was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. Conclusion: The increased expression of ILDR1 is associated with poor prognosis in patients with gastric cancer. ILDR1 can be used as a novel predictive biomarker to provide a new therapeutic target for gastric cancer patients.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4037
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil S. Sahajpal ◽  
Vamsi Kota ◽  
...  

Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer that accounts for almost 85% of lung cancer cases worldwide. Although recent advances in chemotherapy, radiotherapy, and immunotherapy have helped in the clinical management of these patients, the survival rate in advanced stages remains dismal. Furthermore, there is a critical lack of accurate prognostic and stratification markers for emerging immunotherapies. To harness immune response modalities for therapeutic benefits, a detailed understanding of the immune cells in the complex tumor microenvironment (TME) is required. Among the diverse immune cells, natural killer (NK cells) and dendritic cells (DCs) have generated tremendous interest in the scientific community. NK cells play a critical role in tumor immunosurveillance by directly killing malignant cells. DCs link innate and adaptive immune systems by cross-presenting the antigens to T cells. The presence of an immunosuppressive milieu in tumors can lead to inactivation and poor functioning of NK cells and DCs, which results in an adverse outcome for many cancer patients, including those with NSCLC. Recently, clinical intervention using modified NK cells and DCs have shown encouraging response in advanced NSCLC patients. Herein, we will discuss prognostic and predictive aspects of NK cells and DC cells with an emphasis on NSCLC. Additionally, the discussion will extend to potential strategies that seek to enhance the anti-tumor functionality of NK cells and DCs.


2020 ◽  
Author(s):  
Jing Wu ◽  
Hang Cheng ◽  
Tete Li ◽  
Helei Wang ◽  
Guoxia Zang ◽  
...  

Abstract Background: Innate lymphoid cells (ILCs), so far studied mostly in mouse models, are important tissue-resident innate immune cells that play important roles in the colorectal cancer microenvironment and maintain the mucosal tissue homeostasis. Plasmacytoid dendritic cells (pDCs) present complexity in various tumour types and are correlated with poor prognosis. pDCs can promote HIV-1–induced group 3 ILC (ILC3) depletion through the CD95 pathway. However, the role of ILC3s in human colon cancer and their correlation with other immune cells, especially pDCs, remain unclear. Methods: We characterised ILCs and pDCs in the tumour microenvironment of 58 colon cancer patients by flow cytometry and selected three patients for RNA sequencing. Results: ILC3s were negatively correlated, and pDCs were positively correlated, with cancer pathological grade. There was a negative correlation between the numbers of ILC3s and pDCs in tumour tissues. RNA sequencing confirmed the correlations between ILC3s and pDCs and highlighted the potential function of many ILC- and pDC-associated differentially expressed genes in the regulation of tumour immunity. pDCs can induce apoptosis of ILC3s through the CD95 pathway in the tumour microenvironment. Conclusions: One of the interactions between ILC3s and pDCs is via the CD95 pathway, which may help explain the role of ILC3s in colon cancer.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Natalia Barbaro ◽  
Jason Foss ◽  
Sergey Dikalov ◽  
David Harrison ◽  
Annet Kirabo

Recently, it has become apparent that sodium can accumulate in the interstitium of hypertensive humans and animals, and such high salt concentrations drive immune cells toward a pro-inflammatory phenotype through poorly defined mechanisms. We hypothesized that dendritic cells (DCs) are activated by modest elevations of extracellular sodium via formation of IsoLGs leading to hypertension. Isolated mouse splenic DCs were cultured in media with either normal salt (NS, 150 mM NaCl), high salt (HS, 190 mM NaCl) or HS plus the gp91ds-tat peptide which inhibits assembly of NADPH oxidase for 24 hours. DCs exposed to HS demonstrated a marked increase in superoxide production compared to NS (146.3±9.5 vs. 100.0±5.0 % control, p<0.001). This was NADPH oxidase dependent because incubation with the gp91ds-tat peptide prevented this effect. Using flow cytometry, we found that DCs cultured in HS had a significantly higher expression of CD86 and more IsoLG-protein adducts than those cultured in NS. These effects were not mimicked by an equiosmolar concentration of mannitol. Western blot analysis of protein extracts from DCs indicated HS markedly increased phosphorylation of the NADPH oxidase subunit p47 phox and association of p47 phox with gp91 phox . Importantly, we found that the salt-activated DCs promote production of cytokines interferon gamma and interleukin 17 by primed T cells. To determine whether these salt-activated DCs promote hypertension, mice received adoptive transfer of splenic DCs that were cultured for 24 hours in either NS (n = 6); HS (n = 5); or HS plus an IsoLG scavenger (n = 6). Mice were then implanted with radiotelemeters to measure mean arterial pressure (MAP) and infused with a subpressor dose (140 ng/kg/min) of angiotensin II (AngII) for two weeks. This caused no increase in MAP in mice that received NS DCs (+0.8 +/- 3.3 mmHg), whereas MAP increased significantly with AngII infusion in mice that received HS DCs (+13.4 +/- 5 mmHg). This pro-hypertensive effect of salt on DCs was attenuated by scavenging of IsoLGs (-3.3 +/- 4.4 mmHg) during salt exposure. These findings provide a mechanistic link between salt, inflammation and hypertension involving increased oxidative stress and IsoLG production in DCs.


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