scholarly journals Tubulin‐ and actin‐associating GIMAP4 is required for IFN‐γ secretion during Th cell differentiation

2014 ◽  
Vol 93 (2) ◽  
pp. 158-166 ◽  
Author(s):  
Mirkka T Heinonen ◽  
Kartiek Kanduri ◽  
Harri J Lähdesmäki ◽  
Riitta Lahesmaa ◽  
Tiina A Henttinen
Keyword(s):  
Cell Differentiation ◽  
Th Cell ◽  
Ifn Γ

scholarly journals Inhibition of T Helper Cell Type 2 Cell Differentiation and Immunoglobulin E Response by Ligand-Activated Vα14 Natural Killer T Cells

1999 ◽  
Vol 190 (6) ◽  
pp. 783-792 ◽  
Author(s):  
Junqing Cui ◽  
Naohiro Watanabe ◽  
Tetsu Kawano ◽  
Masakatsu Yamashita ◽  
Tohru Kamata ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Natural Killer ◽  
Nkt Cells ◽  
Minor Effect ◽  
Th2 Cell ◽  
Th Cell ◽  
Ifn Γ ◽  
Deficient Mice ◽  
Natural Killer T

Murine Vα14 natural killer T (NKT) cells are thought to play a crucial role in various immune responses, including infectious, allergic, and autoimmune diseases. Because Vα14 NKT cells produce large amounts of both interleukin (IL)-4 and interferon (IFN)-γ upon in vivo stimulation with a specific ligand, α-galactosylceramide (α-GalCer), or after treatment with anti-CD3 antibody, a regulatory role on helper T (Th) cell differentiation has been proposed for these cells. However, the identity of the cytokine produced by Vα14 NKT cells that play a dominant role on the Th cell differentiation still remains controversial. Here, we demonstrate by using Vα14 NKT-deficient mice that Vα14 NKT cells are dispensable for the induction of antigen-specific immunoglobulin (Ig)E responses induced by ovalbumin immunization or Nippostrongylus brasiliensis infection. However, upon in vivo activation with α-GalCer, Vα14 NKT cells are found to suppress antigen-specific IgE production. The suppression appeared to be IgE specific, and was not detected in either Vα14 NKT– or IFN-γ–deficient mice. Consistent with these results, we also found that ligand-activated Vα14 NKT cells inhibited Th2 cell differentiation in an in vitro induction culture system. Thus, it is likely that activated Vα14 NKT cells exert a potent inhibitory effect on Th2 cell differentiation and subsequent IgE production by producing a large amount of IFN-γ. In marked contrast, our studies have revealed that IL-4 produced by Vα14 NKT cells has only a minor effect on Th2 cell differentiation.

scholarly journals Immunomodulatory Effect of Sasa quelpaertensis Leaves Fermentation Products in Mice

Fermentation ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 142
Author(s):  
Ju-Hyun Cho ◽  
Jung-Hyon Kim ◽  
Sunoh Kim ◽  
Hong-Seok Son ◽  
Kwontack Hwang
Keyword(s):  
Ganoderma Lucidum ◽  
Negative Control ◽  
Immunomodulatory Effect ◽  
Leaf Extracts ◽  
Fermentation Products ◽  
Th Cell ◽  
Hericium Erinaceum ◽  
Ifn Γ ◽  
Macrophage Populations ◽  
Different Doses

The purpose of this study was to enhance the immune-enhancing activity of mushroom strains through fermentation to promote food use of leaf extracts of S. quelpaertensis containing β-glucan. We evaluated the immunomodulatory effect of extracts from fermented S. quelpaertensis leaves (SQGL, SQHE, SQPL). S. quelpaertensis leaves fermentation products were prepared by using mushroom mycelia (Ganoderma lucidum, Hericium erinaceum, Phellinus linteus). The content of β-glucan, a major substance in S. quelpaertensis leaves fermentation products, was 3.73 ± 0.50 mg/mL in the extract (SQ) of S. quelpaertensis leaves. The fermented mushrooms, SQGL, were the highest at 5.57 ± 0.86 mg/100 mL, followed by SQHE and SQPL, and the β-glucan content of all of the glucan was >75.3%. To test the immune activity, S. quelpaertensis leaf fermentation products were administered to mice at different doses (60, 160, and 360 mg/kg) for two weeks. Th cell and macrophage populations were found to increase significantly at all three doses compared to the negative control after two weeks. SQGL and SQHE were highest at 160 mg/kg, and SQPL showed the highest Th cell proliferation at 60 mg/kg. In addition, the production of IFN-γ, IL-4, IL-10, and nitric oxide was significantly higher than that of the negative control after two weeks. In particular, an increase was seen at a low concentration of 60 mg/kg. Therefore, the S. quelpaertensis leaf fermentation product can be very useful as a functional ingredient for enhancing immunity.

Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 553-560 ◽  
Author(s):  
Naoki Tokumasa ◽  
Akira Suto ◽  
Shin-ichiro Kagami ◽  
Shunsuke Furuta ◽  
Koichi Hirose ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Differentiation ◽  
Cpg Odn ◽  
T Helper ◽  
Dc Functions ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2−/−) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2−/− DCs. IL-12–induced IFN-γ production was also significantly diminished in Tyk2−/− DCs to levels similar to those in Stat4−/− DCs. Interestingly, Tyk2−/− DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2−/− DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-γ from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.

scholarly journals A Signal Transducer and Activator of  Transcription (Stat)4-independent Pathway for the Development of  T Helper Type 1 Cells

1998 ◽  
Vol 188 (6) ◽  
pp. 1191-1196 ◽  
Author(s):  
Mark H. Kaplan ◽  
Andrea L. Wurster ◽  
Michael J. Grusby
Keyword(s):  
Delayed Type Hypersensitivity ◽  
Th2 Cells ◽  
Signal Transducer ◽  
T Helper ◽  
Th1 Cell ◽  
Th Cells ◽  
Th Cell ◽  
Ifn Γ

The differentiation of T helper (Th) cells is regulated by members of the signal transducer and activator of transcription (STAT) family of signaling molecules. We have generated mice lacking both Stat4 and Stat6 to examine the ability of Th cells to develop in the absence of these two transcription factors. Stat4, Stat6−/− lymphocytes fail to differentiate into interleukin (IL)-4–secreting Th2 cells. However, in contrast to Stat4−/− lymphocytes, T cells from Stat4, Stat6−/− mice produce significant amounts of interferon (IFN)-γ when activated in vitro. Although Stat4, Stat6−/− lymphocytes produce less IFN-γ than IL-12–stimulated control lymphocytes, equivalent numbers of IFN-γ–secreting cells can be generated from cultures of Stat4, Stat6−/− lymphocytes activated under neutral conditions and control lymphocytes activated under Th1 cell–promoting conditions. Moreover, Stat4, Stat6−/− mice are able to mount an in vivo Th1 cell–mediated delayed-type hypersensitivity response. These results support a model of Th cell differentiation in which the generation of Th2 cells requires Stat6, whereas a Stat4-independent pathway exists for the development of Th1 cells.

scholarly journals BHLHE40 Regulates IL-10 and IFN-γ Production in T Cells but Does Not Interfere With Human Type 1 Regulatory T Cell Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Molly Javier Uyeda ◽  
Robert A. Freeborn ◽  
Brandon Cieniewicz ◽  
Rosa Romano ◽  
Ping (Pauline) Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Ex Vivo ◽  
Surface Expression ◽  
Surface Molecules ◽  
Ifn Γ ◽  
And Function ◽  
Tr1 Cells

Type 1 regulatory T (Tr1) cells are subset of peripherally induced antigen-specific regulatory T cells. IL-10 signaling has been shown to be indispensable for polarization and function of Tr1 cells. However, the transcriptional machinery underlying human Tr1 cell differentiation and function is not yet elucidated. To this end, we performed RNA sequencing on ex vivo human CD49b+LAG3+ Tr1 cells. We identified the transcription factor, BHLHE40, to be highly expressed in Tr1 cells. Even though Tr1 cells characteristically produce high levels of IL-10, we found that BHLHE40 represses IL-10 and increases IFN-γ secretion in naïve CD4+ T cells. Through CRISPR/Cas9-mediated knockout, we determined that IL10 significantly increased in the sgBHLHE40-edited cells and BHLHE40 is dispensable for naïve CD4+ T cells to differentiate into Tr1 cells in vitro. Interestingly, BHLHE40 overexpression induces the surface expression of CD49b and LAG3, co-expressed surface molecules attributed to Tr1 cells, but promotes IFN-γ production. Our findings uncover a novel mechanism whereby BHLHE40 acts as a regulator of IL-10 and IFN-γ in human CD4+ T cells.

scholarly journals Recent Insights into CD4+Th Cell Differentiation in Malaria

2018 ◽  
Vol 200 (6) ◽  
pp. 1965-1975 ◽  
Author(s):  
Megan S. F. Soon ◽  
Ashraful Haque
Keyword(s):  
Cell Differentiation ◽  
Th Cell

scholarly journals IL-15 Generates IFN-γ-producing Cells Reciprocally Expressing Lymphoid-Myeloid Markers during Dendritic Cell Differentiation

2019 ◽  
Vol 15 (2) ◽  
pp. 464-480 ◽  
Author(s):  
Kee Woong Kwon ◽  
So Jeong Kim ◽  
Hongmin Kim ◽  
Woo Sik Kim ◽  
Soon Myung Kang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Dendritic Cell ◽  
Dendritic Cell Differentiation ◽  
Ifn Γ
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