scholarly journals Cytokine regulation of stem cells

Author(s):  
Gyanesh Singh ◽  
Hasan Korkaya

Different types of stem cells are targeted by a number of cytokines that alter proliferation, differentiation, or other properties of stem cells. Stem cells are known to express various cytokine genes. As IL-12, IL-14, G-CSF, and GM-CSF expression is lost after the differentiation of MSCs, these factors might have major contribution to pluripotency. Several other cytokines that are produced by immune cells, frequently target stem cells. Modulation of stem cell functions by cytokines can be a cause of various diseases including cancer. Stem cells can show immunosuppressive properties by a number of mechanisms. MSC-induced immunosuppression is often mediated by IFN-γ, TNF-α, IL-1α, or IL-1β. In co-culture experiments, MSCs were able to control T cells IL-2 response, or, dendritic cells TNF-α and IL-10 secretion. MSCs are also known to cause decreased interferon γ (IFN-γ) and increased IL-4 production by immune cells. However, the outcome in most of the cases depends on the presence of various factors that might synergize or antagonize with each other.

2016 ◽  
Author(s):  
Gyanesh Singh ◽  
Hasan Korkaya

Different types of stem cells are targeted by a number of cytokines that alter proliferation, differentiation, or other properties of stem cells. Stem cells are known to express various cytokine genes. As IL-12, IL-14, G-CSF, and GM-CSF expression is lost after the differentiation of MSCs, these factors might have major contribution to pluripotency. Several other cytokines that are produced by immune cells, frequently target stem cells. Modulation of stem cell functions by cytokines can be a cause of various diseases including cancer. Stem cells can show immunosuppressive properties by a number of mechanisms. MSC-induced immunosuppression is often mediated by IFN-γ, TNF-α, IL-1α, or IL-1β. In co-culture experiments, MSCs were able to control T cells IL-2 response, or, dendritic cells TNF-α and IL-10 secretion. MSCs are also known to cause decreased interferon γ (IFN-γ) and increased IL-4 production by immune cells. However, the outcome in most of the cases depends on the presence of various factors that might synergize or antagonize with each other.


Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Yves Delneste ◽  
Peggy Charbonnier ◽  
Nathalie Herbault ◽  
Giovanni Magistrelli ◽  
Gersende Caron ◽  
...  

Abstract Human monocytes differentiate into dendritic cells (DCs) or macrophages according to the nature of environmental signals. Monocytes stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin 4 (IL-4) yield DCs. We tested here whether interferon-γ (IFN-γ), a potent activator of macrophages, may modulate monocyte differentiation. Addition of IFN-γ to IL-4 plus GM-CSF–stimulated monocytes switches their differentiation from DCs to CD14−CD64+ macrophages. IFN-γ increases macrophage colony-stimulating factor (M-CSF) and IL-6 production by IL-4 plus GM-CSF–stimulated monocytes by acting at the transcriptional level and acts together with IL-4 to up-regulate M-CSF but not IL-6 production. IFN-γ also increases M-CSF receptor internalization. Results from neutralizing experiments show that both M-CSF and IL-6 are involved in the ability of IFN-γ to skew monocyte differentiation from DCs to macrophages. Finally, this effect of IFN-γ is limited to early stages of differentiation. When added to immature DCs, IFN-γ up-regulates IL-6 but not M-CSF production and does not convert them to macrophages, even in the presence of exogenous M-CSF. In conclusion, IFN-γ shifts monocyte differentiation to macrophages rather than DCs through autocrine M-CSF and IL-6 production. These data show that IFN-γ controls the differentiation of antigen-presenting cells and thereby reveals a new mechanism by which IFN-γ orchestrates the outcome of specific immune responses.


2020 ◽  
Author(s):  
Zhicheng Zhang ◽  
Guo Ai ◽  
Liping Chen ◽  
Shunfang Liu ◽  
Chen Gong ◽  
...  

Abstract Background: We aim to explore the association of immunological features with COVID-19 severity.Methods: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature.Results: A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of some immune cells, CD3+ T cell (×106, MD, -413.87; 95%CI, -611.39 to -216.34), CD4+ T cell (×106, MD, -203.56; 95%CI, -277.94 to -129.18), CD8+ T cell (×106, MD, -128.88; 95%CI, -163.97 to -93.79), B cell (×106/L; MD, -23.87; 95%CI, -43.97 to -3.78) and NK cell (×106/L; MD, -57.12; 95%CI, -81.18 to -33.06), and significantly higher levels of some cytokines, TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of some chemokines, MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant differences were found in other indicators, Treg cell (×106, MD, -0.13; 95%CI, -1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, -0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, -0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, -0.49 to 0.60), IL-4 (pg/ml; MD, -0.03; 95%CI, -0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, -0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, -2.88 to 4.75).Conclusion: Our meta-analysis revealed significant lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), significant higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and significant higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases compared with mild cases of COVID-19. Measurement of immunological features could help to assess disease severity for effective triage of COVID-19 patients.


2019 ◽  
Vol 41 (1) ◽  
Author(s):  
Nguyen Thu Thuy ◽  
Nguyen Thi Xuan

IL-10 is an anti-inflammatory cytokine, participating in induction of immune tolerance and cell apoptotic death. Dendritic cells (DCs) is the most professional antigen-presenting cells among innate immune cells to exert generation and maintenance of immunological memory mediated through activation of T and B lymphocytes. The STAT signalling pathway plays a regulatory role of maturation and differentiation of immune cells. In this study, DCs were treated with inflammatory cytokines including TNF-a, INFg, IL-2 and IL-10 and subsequently examined the phosphorylation of STAT-1 and STAT-3, TNF-α concetration in cell suspension and the proportion of Annexin V+ and caspase 3+ cells. Methods used for this investigation include western blotting, flow cytometry and ELISA. DCs were derived from mouse bone marrow cells and cultured with GM-CSF for 8 days. As a result, IL-10, but not other cytokines enhanced the number of Annexin V+cells and caspase 3 activity in DCs. More importantly, IL-10 also increased the phosphorylation of STAT-1 as well as the release of TNF-α into cell suspension. In conclusion, activation of STAT-1 might relate to the cell apoptotic death and TNF-α sectetion in IL-10-treated DCs.


2019 ◽  
Vol 41 (1) ◽  
Author(s):  
Xuan Thi Nguyen ◽  
Phuong Thi Hoai Bach ◽  
Thuy Thu Nguyen

IL-10 is an anti-inflammatory cytokine, participating in induction of immune tolerance and cell apoptotic death. Dendritic cells (DCs) is the most professional antigen-presenting cells among innate immune cells to exert generation and maintenance of immunological memory mediated through activation of T and B lymphocytes. The STAT signalling pathway plays a regulatory role of maturation and differentiation of immune cells. In this study, DCs were treated with inflammatory cytokines including TNF-, INF, IL-2 and IL-10 and subsequently examined the phosphorylation of STAT-1 and STAT-3, TNF-α concetration in cell suspension and percents of Annexin V+ and caspase 3+ cells. Methods used for this investigation include western blotting, flow cytometry and ELISA. DCs were derived from mouse bone marrow cells and cultured with GM-CSF for 8 days. As a result, IL-10, but not other cytokines enhanced the number of Annexin V+cells and caspase 3 activity in DCs. More importantly, IL-10 also increased the phosphorylation of STAT-1 as well as the release of TNF-α into cell suspension. In conclusion, activation of STAT-1 might relate to the cell apoptotic death and TNF-α sectetion in IL-10-treated DCs.


2021 ◽  
Vol 7 (3) ◽  
pp. 205521732110323
Author(s):  
Kouichi Ito ◽  
Naoko Ito ◽  
Sudhir K Yadav ◽  
Shradha Suresh ◽  
Yong Lin ◽  
...  

Background Many RRMS patients who had been treated for over 20 years with GA 20 mg/ml daily (GA20) switched to 40 mg/ml three times-a-week (GA40) to reduce injection-related adverse events. Although GA40 is as effective as GA20 in reducing annualized relapse rate and MRI activity, it remains unknown how switching to GA40 from GA20 affects the development of pathogenic and regulatory immune cells. Objective To investigate the difference in immunological parameters in response to GA20 and GA40 treatments. Methods We analyzed five pro-inflammatory cytokines (IL-1β, IL-23, IL-12, IL-18, TNF-α), and three anti-inflammatory/regulatory cytokines (IL-10, IL-13, and IL-27) in serum. In addition, we analyzed six cytokines (IFN-γ, IL-17A, GM-CSF, IL-10, IL-6, and IL-27) in cultured PBMC supernatants. The development of Th1, Th17, Foxp3 Tregs, M1-like, and M2-like macrophages were examined by flow cytometry. Samples were analyzed before and 12 months post switching to GA40 or GA20. Results Pro- and anti-inflammatory cytokines were comparable between the GA40 and GA20 groups. Development of Th1, Th17, M1-like macrophages, M2-like macrophages, and Foxp3 Tregs was also comparable between the two groups. Conclusions The immunological parameters measured in RRMS patients treated with GA40 three times weekly are largely comparable to those given daily GA20 treatment.


Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2489-2497 ◽  
Author(s):  
Mark B. Faries ◽  
Isabelle Bedrosian ◽  
Shuwen Xu ◽  
Gary Koski ◽  
James G. Roros ◽  
...  

Abstract Mature dendritic cells (DCs), in addition to providing costimulation, can define the Th1, in contrast to the Th2, nature of a T-cell response through the production of cytokines and chemokines. Because calcium signaling alone causes rapid DC maturation of both normal and transformed myeloid cells, it was evaluated whether calcium-mobilized DCs polarize T cells toward a Th1 or a Th2 phenotype. After human monocytes were cultured for 24 hours in serum-free medium and granulocyte-macrophage colony-stimulating factor to produce immature DCs, additional overnight culture with either calcium ionophore (CI) or interferon γ (IFN-γ), tumor necrosis factor-α (TNF-α), and soluble CD40L resulted in phenotypically mature DCs that produced interleukin-8 (IL-8) and displayed marked expression of CD80, CD86, CD40, CD54, CD83, DC-LAMP, and RelB. DCs matured by IFN-γ, TNF-α, and soluble CD40L were additionally distinguished by undetectable CD4 expression, marked secretion of IL-12, IL-6, and MIP-1β, and preferential ability to promote Th1/Tc1 characteristics during T-cell sensitization. In contrast, DCs matured by CI treatment were distinguished by CD4 expression, modest or absent levels of IL-12, IL-6, and MIP-1β, and preferential ability to promote Th2/Tc2 characteristics. Calcium signaling selectively antagonized IL-12 production by mature DCs activated with IFN-γ, TNF-α, and soluble CD40L. Although the activation of DCs by calcium signals is largely mediated through calcineurin phosphatase, the inhibition of IL-12 production by calcium signaling was independent of this enzyme. Naturally occurring calcium fluxes in immature DCs, therefore, negatively regulate Dc1 differentiation while promoting Dc2 characteristics and Th2/Tc2 polarization. Calcium-mobilized DCs may have clinical usefulness in treating disease states with excessive Th1/Tc1 activity, such as graft-versus-host disease or autoimmunity.


2021 ◽  
Vol 15 (6) ◽  
pp. 1130-1131
Author(s):  
S. Z. A. Shah ◽  
B. R. Devrajani ◽  
N. A. Lashari

During December 2019 at Wuhan the SARS-CoV-2 epidemic emerged and rapidly occupies the entire world, present as pandemic responsible for pulmonary dysfunction like acute respiratory distress syndrome and pneumonia but with time clinicians and researchers have been found some extrapulmonary features of COVID-19 which may reflect either replication or dissemination of SARS-CoV-2 infection as widespread immunopathological sequelae1. The knowledge regarding extrapulmonary complexities in the hospitalized COVID-19 patients should be addressed to prevent and decrease the coincidental exposure2. The spike protein and ACE2 receptors through S protein and MPRSS2 play role in pathogenesis of SARS-CoV-2 infection3. ACE2 receptors are situated in heart, GI epithelium, alveolar II cells, vessels, renal and smooth muscles of entire body responsible for COVID-19 induced injury4,5. SARS-COV-2 actuates T lymphocytes via cytokines: interleukin (IL-1 and 6), GM-CSF, and interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) known as cytokine storm bringing about tissue injury6.


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