Regulation of apoptosis by IL-10 and the association with STAT-1 signaling molecule in dendritic cells

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.

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Regulation of apoptosis of dendritic cells by il-10 and in association with stat-1 signaling molecule

TAP CHI SINH HOC ◽

10.15625/0866-7160/v41n1.12607 ◽

2019 ◽

Vol 41 (1) ◽

Author(s):

Nguyen Thu Thuy ◽

Nguyen Thi Xuan

Keyword(s):

Dendritic Cells ◽

Cell Suspension ◽

Immune Cells ◽

Caspase 3 ◽

Bone Marrow Cells ◽

Annexin V ◽

Mouse Bone Marrow ◽

Gm Csf ◽

Apoptotic Death ◽

Tnf Α

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.

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Cytokine regulation of stem cells

10.7287/peerj.preprints.2347 ◽

2016 ◽

Author(s):

Gyanesh Singh ◽

Hasan Korkaya

Keyword(s):

Stem Cells ◽

Dendritic Cells ◽

Stem Cell ◽

Immune Cells ◽

Interferon Γ ◽

Gm Csf ◽

Cell Functions ◽

Tnf Α ◽

Different Types ◽

Ifn Γ

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.

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Cytokine regulation of stem cells

10.7287/peerj.preprints.2347v1 ◽

2016 ◽

Author(s):

Gyanesh Singh ◽

Hasan Korkaya

Keyword(s):

Stem Cells ◽

Dendritic Cells ◽

Stem Cell ◽

Immune Cells ◽

Interferon Γ ◽

Gm Csf ◽

Cell Functions ◽

Tnf Α ◽

Different Types ◽

Ifn Γ

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TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens

Nature Communications ◽

10.1038/s41467-020-20307-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Rikio Yabe ◽

Soo-Hyun Chung ◽

Masanori A. Murayama ◽

Sachiko Kubo ◽

Kenji Shimizu ◽

...

Keyword(s):

Dendritic Cells ◽

Bone Marrow Cells ◽

Dendritic Cell Maturation ◽

Mouse Bone Marrow ◽

Gm Csf ◽

Good Target ◽

Antigen Presenting ◽

Dc Maturation

AbstractTARM1 is a member of the leukocyte immunoglobulin-like receptor family and stimulates macrophages and neutrophils in vitro by associating with FcRγ. However, the function of this molecule in the regulation of the immune system is unclear. Here, we show that Tarm1 expression is elevated in the joints of rheumatoid arthritis mouse models, and the development of collagen-induced arthritis (CIA) is suppressed in Tarm1–/– mice. T cell priming against type 2 collagen is suppressed in Tarm1–/– mice and antigen-presenting ability of GM-CSF-induced dendritic cells (GM-DCs) from Tarm1–/– mouse bone marrow cells is impaired. We show that type 2 collagen is a functional ligand for TARM1 on GM-DCs and promotes DC maturation. Furthermore, soluble TARM1-Fc and TARM1-Flag inhibit DC maturation and administration of TARM1-Fc blocks the progression of CIA in mice. These results indicate that TARM1 is an important stimulating factor of dendritic cell maturation and could be a good target for the treatment of autoimmune diseases.

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Faculty Opinions recommendation of GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c(+)MHCII(+) Macrophages and Dendritic Cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725566020.793507731 ◽

2015 ◽

Author(s):

Clotilde Théry ◽

Elodie Segura

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Heterogeneous Population ◽

Mouse Bone Marrow ◽

Gm Csf ◽

Bone Marrow Cultures ◽

Marrow Cultures

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J-LEAPS Vaccines Mature Mouse Bone Marrow Cells to Dendritic Cells-1 (DC1) which can Deliver Protective Immunity

Clinical Immunology ◽

10.1016/j.clim.2010.03.098 ◽

2010 ◽

Vol 135 ◽

pp. S32

Author(s):

Patricia Taylor ◽

Gary Koski ◽

Erin Bailey ◽

Daniel Zimmerman ◽

Ken S. Rosenthal

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Protective Immunity ◽

Bone Marrow Cells ◽

Mouse Bone Marrow ◽

Mature Mouse ◽

Mouse Bone Marrow Cells ◽

Marrow Cells

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Differentiation of Dendritic Cells in Cultures of Rat and Mouse Bone Marrow Cells

Advances in Experimental Medicine and Biology - Dendritic Cells in Fundamental and Clinical Immunology ◽

10.1007/978-1-4615-2930-9_42 ◽

1993 ◽

pp. 251-255 ◽

Cited By ~ 2

Author(s):

William E. Bowers ◽

Shengqiang Yu ◽

Syeedur Khandkar

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Bone Marrow Cells ◽

Mouse Bone Marrow ◽

Mouse Bone Marrow Cells ◽

Marrow Cells

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Heme-stress activated NRF2 skews fate trajectories of bone marrow cells from dendritic cells towards red pulp-like macrophages in hemolytic anemia

Cell Death and Differentiation ◽

10.1038/s41418-022-00932-1 ◽

2022 ◽

Author(s):

Florence Vallelian ◽

Raphael M. Buzzi ◽

Marc Pfefferlé ◽

Ayla Yalamanoglu ◽

Irina L. Dubach ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Dendritic Cell ◽

Sickle Cell Disease ◽

Bone Marrow Cells ◽

Cell Disease ◽

Secondary Immunodeficiency ◽

Gm Csf ◽

Bone Marrow Cultures ◽

Marrow Cultures

AbstractHeme is an erythrocyte-derived toxin that drives disease progression in hemolytic anemias, such as sickle cell disease. During hemolysis, specialized bone marrow-derived macrophages with a high heme-metabolism capacity orchestrate disease adaptation by removing damaged erythrocytes and heme-protein complexes from the blood and supporting iron recycling for erythropoiesis. Since chronic heme-stress is noxious for macrophages, erythrophagocytes in the spleen are continuously replenished from bone marrow-derived progenitors. Here, we hypothesized that adaptation to heme stress progressively shifts differentiation trajectories of bone marrow progenitors to expand the capacity of heme-handling monocyte-derived macrophages at the expense of the homeostatic generation of dendritic cells, which emerge from shared myeloid precursors. This heme-induced redirection of differentiation trajectories may contribute to hemolysis-induced secondary immunodeficiency. We performed single-cell RNA-sequencing with directional RNA velocity analysis of GM-CSF-supplemented mouse bone marrow cultures to assess myeloid differentiation under heme stress. We found that heme-activated NRF2 signaling shifted the differentiation of bone marrow cells towards antioxidant, iron-recycling macrophages, suppressing the generation of dendritic cells in heme-exposed bone marrow cultures. Heme eliminated the capacity of GM-CSF-supplemented bone marrow cultures to activate antigen-specific CD4 T cells. The generation of functionally competent dendritic cells was restored by NRF2 loss. The heme-induced phenotype of macrophage expansion with concurrent dendritic cell depletion was reproduced in hemolytic mice with sickle cell disease and spherocytosis and associated with reduced dendritic cell functions in the spleen. Our data provide a novel mechanistic underpinning of hemolytic stress as a driver of hyposplenism-related secondary immunodeficiency.

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