scholarly journals Proprotein convertase furin is preferentially expressed in T helper 1 cells and regulates interferon gamma

Blood ◽  
2006 ◽  
Vol 108 (3) ◽  
pp. 983-985 ◽  
Author(s):  
Marko Pesu ◽  
Linda Muul ◽  
Yuka Kanno ◽  
John J. O'Shea
Keyword(s):  
Interferon Gamma ◽  
Interleukin 12 ◽  
Th1 Cells ◽  
Dependent Manner ◽  
T Helper ◽  
Proprotein Convertase ◽  
T Helper 1 ◽  
Ifn Γ ◽  
Induced Genes ◽  
And Control

Abstract Interleukin 12 (IL-12) is a major inducer of interferon gamma (IFN-γ) and the principal mediator of T helper 1 (Th1) differentiation. To identify IL-12–regulated genes, which might contribute to Th1 differentiation and IFNG regulation, we employed microarray analysis. Surprisingly, a ubiquitously expressed proprotein convertase (PC), furin, was one of the most consistently IL-12–induced genes in T cells, and among PCs was the only one regulated by this cytokine. Furin was preferentially expressed in differentiated Th1 cells in a Stat4-dependent manner. Expression of furin enhanced IFN-γ secretion, whereas inhibition of furin interfered with IFN-γ production. Thus, we conclude that IL-12 induction of furin might represent a new aspect of IFN-γ regulation and control of Th1 differentiation.

scholarly journals Immediate Interferon Gamma Induction Determines Murine Host Compatibility Differences between Toxoplasma gondii and Neospora caninum

2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Rachel S. Coombs ◽  
Matthew L. Blank ◽  
Elizabeth D. English ◽  
Yaw Adomako-Ankomah ◽  
Ifeanyi-Chukwu Samuel Urama ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Interferon Gamma ◽  
Neospora Caninum ◽  
Ectopic Expression ◽  
Parasite Burden ◽  
Interleukin 12 ◽  
Content Type ◽  
Ifn Γ ◽  
And Control

ABSTRACT Rodents are critical for the transmission of Toxoplasma gondii to the definitive feline host via predation, and this relationship has been extensively studied as a model for immune responses to parasites. Neospora caninum is a closely related coccidian parasite of ruminants and canines but is not naturally transmitted by rodents. We compared mouse innate immune responses to N. caninum and T. gondii and found marked differences in cytokine levels and parasite growth kinetics during the first 24 h postinfection (hpi). N. caninum-infected mice produced significantly higher levels of interleukin-12 (IL-12) and interferon gamma (IFN-γ) by as early as 4 hpi, but the level of IFN-γ was significantly lower or undetectable in T. gondii-infected mice during the first 24 hpi. “Immediate” IFN-γ and IL-12p40 production was not detected in MyD88−/− mice. However, unlike IL-12p40−/− and IFN-γ−/− mice, MyD88−/− mice survived N. caninum infections at the dose used in this study. Serial measures of parasite burden showed that MyD88−/− mice were more susceptible to N. caninum infections than wild-type (WT) mice, and control of parasite burdens correlated with a pulse of serum IFN-γ at 3 to 4 days postinfection in the absence of detectable IL-12. Immediate IFN-γ was partially dependent on the T. gondii mouse profilin receptor Toll-like receptor 11 (TLR11), but the ectopic expression of N. caninum profilin in T. gondii had no impact on early IFN-γ production or parasite proliferation. Our data indicate that T. gondii is capable of evading host detection during the first hours after infection, while N. caninum is not, and this is likely due to the early MyD88-dependent recognition of ligands other than profilin.

scholarly journals Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3120
Author(s):  
Jae Jeon ◽  
Byung-Cheol Lee ◽  
Doman Kim ◽  
Daeho Cho ◽  
Tae Kim
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Biological Activities ◽  
Water Soluble ◽  
Th1 Cells ◽  
Dependent Manner ◽  
T Helper ◽  
Th1 Cell ◽  
Ifn Γ

A flavonoid Astragalin (kaempferol-3-O-β-d-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O-β-d-isomaltotrioside, Ast-Gal) on murine bone marrow-derived dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through the upregulation of surface markers, such as cluster of differentiation (CD)80, CD86, and Major histocompatibility complex (MHC) II in a dose-dependent manner, while Ast had little effects. Additionally, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as interleukin (IL)-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4+ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4+ T cells into Th1 cells. The addition of neutralizing IL-12 monoclonal antibody (mAb) to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly decreased interferon (IFN)-γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

scholarly journals Selective Expression of an Interleukin-12 Receptor Component by Human T Helper 1 Cells

1997 ◽  
Vol 185 (5) ◽  
pp. 825-832 ◽  
Author(s):  
Lars Rogge ◽  
Luisella Barberis-Maino ◽  
Mauro Biffi ◽  
Nadia Passini ◽  
David H. Presky ◽  
...  
Keyword(s):  
Interleukin 12 ◽  
Type I ◽  
T Helper ◽  
T Helper 1 ◽  
Receptor Component ◽  
Selective Expression ◽  
Ifn Γ ◽  
Activated Monocytes ◽  
Th2 Differentiation

Interleukin-12 (IL-12), a heterodimeric cytokine produced by activated monocytes and dendritic cells, plays a crucial role in regulating interferon (IFN)-γ production and in the generation of IFN–γ–producing T helper 1 (Th1) cells. Here we show that the IL-12 receptor (IL12R) β2 subunit, a recently cloned binding and signal transducing component of the IL-12R, is expressed on human Th1 but not Th2 clones and is induced during differentiation of human naive cells along the Th1 but not the Th2 pathway. IL-12 and type I but not type II interferons induce expression of the IL-12R β2 chain during in vitro T cell differentiation after antigen receptor triggering. The selective expression and regulation of the IL-12R β2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1/Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies.

scholarly journals T Helper Type 2 Cell Differentiation Occurs in the Presence of Interleukin 12 Receptor β2 Chain Expression and Signaling

2000 ◽  
Vol 191 (5) ◽  
pp. 847-858 ◽  
Author(s):  
Ryuta Nishikomori ◽  
Rolf O. Ehrhardt ◽  
Warren Strober
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Th2 Cells ◽  
Interleukin 12 ◽  
Th1 Cells ◽  
T Helper ◽  
Ifn Γ ◽  
Helper Type

The differentiation of CD4+ T cells into T helper type 1 (Th1) cells is driven by interleukin (IL)-12 through the IL-12 receptor β2 (IL-12Rβ2) chain, whereas differentiation into Th2 cells is driven by IL-4, which downregulates IL-12Rβ2 chain. We reexamined such differentiation using IL-12Rβ2 chain transgenic mice. We found that CD4+ T cells from such mice were able to differentiate into Th2 cells when primed with IL-4 or IL-4 plus IL-12. In the latter case, the presence of IL-4 suppressed interferon (IFN)-γ production 10–100-fold compared with cells cultured in IL-12 alone. Finally, in studies of the ability of IL-12 to convert Th2 cells bearing a competent IL-12R to the Th1 cells, we showed that: (a) T cells bearing the IL-12Rβ2 chain transgene and primed under Th2 conditions could not be converted to Th1 cells by repeated restimulation under Th1 conditions; and (b) established Th2 clones transfected with the IL-12Rβ2 chain construct continued to produce IL-4 when cultured with IL-12. These studies show that IL-4–driven Th2 differentiation can occur in the presence of persistent IL-12 signaling and that IL-4 inhibits IFN-γ production under these circumstances. They also show that established Th2 cells cannot be converted to Th1 cells via IL-12 signaling.

scholarly journals Pengaruh Vaksinasi BCG Terhadap Serum Interferon Gamma pada Kasus Asma Ekstrinsik Atopi Anak

Sari Pediatri ◽  
2016 ◽  
Vol 10 (3) ◽  
pp. 207
Author(s):  
Yolanda Olivia Palandeng ◽  
Diana Devi Takumansang Sondakh
Keyword(s):  
Interferon Gamma ◽  
Control Group ◽  
T Helper ◽  
T Helper 1 ◽  
Control Group Design ◽  
T Helper 2 ◽  
Group Design ◽  
Ifn Γ

Latar belakang. Prevalensi asma makin meningkat, diduga berkaitan dengan kejadian infeksi pada anak yang menurun sehingga menyebabkan pergeseran keseimbangan antara limfosit T helper 1 (Th1) dan T helper 2 (Th2) ke arah predominan Th2. Infeksi mikobakterium dan vaksinasi BCG dapat meningkatkan respon imun Th1 (interferon gamma (IFN-γ)) dan menekan Th2.Tujuan. Mengetahui pengaruh vaksinasi BCG terhadap kadar IFN-γ serum pasien asma ekstrinsik atopi anak setelah vaksinasi BCG satu kali.Metode. Penelitian kuasi-eksperimental pretest posttest control group design pada anak asma atopi. Pengacakan perlakuan dilakukan terhadap subjek ke dalam kelompok BCG dan plasebo. Sebelum dan 8 minggu sesudah perlakuan diukur kadar IFN-γ serum.Hasil. Kadar IFN-γ serum tidak meningkat sesudah vaksinasi BCG (median 1,580 dan 0,780 pg/ml, p= 0,326) dan plasebo (median 1,255 dan 0,670 pg/ml, p= 0,079). Selisih kadar IFN-γ serum kelompok BCG dan plasebo tidak berbeda bermakna (median 0,020 dan -0,420 pg/ml, p= 0,449).Kesimpulan. Kadar IFN-γ serum pasien asma ekstrinsik atopi anak tidak meningkat setelah vaksinasi BCG 1 kali.

scholarly journals Suppression of Staphylococcus aureus Superantigen-Independent Interferon Gamma Response by a Probiotic Polysaccharide

2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Wonbeom Paik ◽  
Francis Alonzo ◽  
Katherine L. Knight
Keyword(s):  
Staphylococcus Aureus ◽  
Bloodstream Infection ◽  
Interferon Gamma ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Interleukin 12 ◽  
Dependent Manner ◽  
Content Type ◽  
Ifn Γ

ABSTRACT Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes a variety of diseases. Bloodstream infection is the most severe, with mortality rates reaching 20 to 50%. Exopolysaccharide (EPS) from the probiotic Bacillus subtilis reduces bacterial burden and inflammation during S. aureus bloodstream infection in mice. Protection is due, in part, to hybrid macrophages that restrict S. aureus growth through reactive oxygen species and to limiting superantigen-induced T cell activation and interferon gamma (IFN-γ) production during infection. A decrease in IFN-γ production was observed within 24 h after infection, and here, we investigated how EPS abrogates its production. We discovered that S. aureus uses a rapid, superantigen-independent mechanism to induce host IFN-γ and that this is mediated by interleukin-12 (IL-12) activation of NK cells. Furthermore, we found that EPS limits IFN-γ production by modulating host immunity in a Toll-like receptor 4 (TLR4)-dependent manner, a signaling pathway that is required for EPS-mediated protection from S. aureus infection in vivo. We conclude that EPS protects hosts from acute bloodstream S. aureus infection not only by inducing macrophages that restrict S. aureus growth and inhibit superantigen-activated T cells but also by limiting NK cell production of IFN-γ after S. aureus infection in a TLR4-dependent manner.

scholarly journals Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

2018 ◽  
Author(s):  
Jae Hyoung Jeon ◽  
Byung-Cheol Lee ◽  
Doman Kim ◽  
Daeho Cho ◽  
Tae Sung Kim
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Biological Activities ◽  
Water Soluble ◽  
Th1 Cells ◽  
Dependent Manner ◽  
T Helper ◽  
Th1 Cell ◽  
Ifn Γ

A flavonoid Astragalin (kaempferol-3-O-β-D-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O- β-D-isomaltotrioside, Ast-Gal) on dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through up-regulation of surface markers, such as CD80, CD86, and MHC II in a dose-dependent manner, while Ast had little effects. Also, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as IL-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4+ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4+ T cells into Th1 cells. The addition of neutralizing IL-12 mAb to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly increased IFN- γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs, and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

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