scholarly journals T helper type 1–specific Brg1 recruitment and remodeling of nucleosomes positioned at the IFN-γ promoter are Stat4 dependent

2006 ◽  
Vol 203 (6) ◽  
pp. 1493-1505 ◽  
Author(s):  
Fuping Zhang ◽  
Mark Boothby
Keyword(s):  
Interferon Γ ◽  
T Cell Differentiation ◽  
T Helper ◽  
Nucleosome Remodeling ◽  
Specific Manner ◽  
Ifn Γ ◽  
Calcineurin Phosphatase ◽  
Th2 Differentiation ◽  
Early Recruitment

Transcriptional competence of the interferon-γ (IFN-γ) locus is enhanced as Th1 effectors develop from naive CD4 T lymphocytes; conversely, this gene is repressed during Th2 differentiation. We now show that the Switch (Swi)–sucrose nonfermenter (SNF) component Brahma-related gene 1 (Brg1) is recruited, and positioned nucleosomes are remodeled, in a Th1-specific manner that is dependent on the transcription factor Stat4 and calcineurin phosphatase activity. Interference with specific components of mammalian Swi–SNF complexes decreased CD4 T cell differentiation into IFN-γ–positive Th1 cells. These findings reveal a collaborative mechanism of IFN-γ gene regulation during Th1 differentiation and suggest that a Th1-specific chromatin structure is created by early recruitment of Swi–SNF complexes and nucleosome remodeling dependent on Stat4 and calcineurin activation.

scholarly journals Interferon γ Stabilizes the T Helper Cell Type 1 Phenotype

2001 ◽  
Vol 194 (2) ◽  
pp. 165-172 ◽  
Author(s):  
Yongkang Zhang ◽  
Ron Apilado ◽  
John Coleman ◽  
Shlomo Ben-Sasson ◽  
Sharon Tsang ◽  
...  
Keyword(s):  
Critical Role ◽  
Interferon Γ ◽  
T Helper Cell ◽  
Helper Cell ◽  
Wild Type ◽  
T Helper ◽  
Helper Cell Type ◽  
Ifn Γ ◽  
Th 1

T helper cell (Th)1-primed CD4 T cells from wild-type donors make little interleukin (IL)-4 when restimulated under Th2 conditions. However, such restimulation of Th1-primed cells from interferon (IFN)-γ2/− or IFN-γ receptor (IFN-γR)−/− mice resulted in substantial production of IL-4 and other Th2 cytokines. Adding IFN-γ to the priming culture markedly diminished the capacity of Th1-primed IFN-γ2/− cells to express IL-4. Even IFN-γ–producing cells from IFN-γR−/− mice could acquire IL-4–producing capacity. Thus, IFN-γ is not required for the development of IFN-γ–producing capacity, but it plays a critical role in suppressing the IL-4–producing potential of Th1 cells.

scholarly journals Interleukin 12 Protects from a T Helper Type 1–mediated Autoimmune Disease, Experimental Autoimmune Uveitis, through a Mechanism Involving Interferon γ, Nitric Oxide, and Apoptosis

1999 ◽  
Vol 189 (2) ◽  
pp. 219-230 ◽  
Author(s):  
Teresa K. Tarrant ◽  
Phyllis B. Silver ◽  
Jennifer L. Wahlsten ◽  
Luiz V. Rizzo ◽  
Chi-Chao Chan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Interferon Γ ◽  
Effector T Cells ◽  
T Helper ◽  
Experimental Autoimmune Uveitis ◽  
Ifn Γ ◽  
Helper Type ◽  
Experimental Autoimmune

Pathogenic effector T cells in experimental autoimmune uveitis (EAU) are T helper type 1–like, and interleukin (IL)-12 is required for their generation and function. Therefore, we expected that IL-12 administration would have disease-enhancing effects. Mice were immunized with a uveitogenic regimen of the retinal antigen interphotoreceptor retinoid-binding protein, treated with IL-12 (100 ng/d for 5 d), and EAU was assessed by histopathology. Unexpectedly, IL-12 treatment failed to enhance EAU in resistant strains and downregulated disease in susceptible strains. Only treatment during the first, but not during the second, week after immunization was consistently protective. High levels of interferon γ (IFN-γ) were present in the serum during IL-12 treatment, but subsequent antigen-specific IFN-γ production in protected mice was diminished, as were IL-5 production, lymph node cell proliferation, and serum antibody levels. Treated mice had fewer cells and evidence of enhanced apoptosis in the draining lymph nodes. Unlike wild-type mice, IFN-γ–deficient, inducible nitric oxide synthase (iNOS)-deficient, and Bcl-2lck transgenic mice were poorly protected by IL-12, whereas IL-10–deficient mice were protected. We conclude that administration of IL-12 aborts disease by curtailing development of uveitogenic effector T cells. The data are compatible with the interpretation that IL-12 induces systemic hyperinduction of IFN-γ, causing activation of iNOS and production of NO, which mediates protection at least in part by triggering Bcl-2 regulated apoptotic deletion of the antigen-specific T cells as they are being primed.

scholarly journals Interferon γ Derived from CD4+ T Cells Is Sufficient to Mediate T Helper Cell Type 1 Development

1998 ◽  
Vol 188 (9) ◽  
pp. 1651-1656 ◽  
Author(s):  
Adil E. Wakil ◽  
Zhi-En Wang ◽  
James C. Ryan ◽  
Deborah J. Fowell ◽  
Richard M. Locksley
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Interferon Γ ◽  
Receptor Expression ◽  
Interleukin 12 ◽  
T Helper ◽  
Activated T Cells ◽  
Ifn Γ

Interferon γ (IFN-γ) has been implicated in T helper type 1 (Th1) cell development through its ability to optimize interleukin 12 (IL-12) production from macrophages and IL-12 receptor expression on activated T cells. Various systems have suggested a role for IFN-γ derived from the innate immune system, particularly natural killer (NK) cells, in mediating Th1 differentiation in vivo. We tested this requirement by reconstituting T cell and IFN-γ doubly deficient mice with wild-type CD4+ T cells and challenging the mice with pathogens that elicited either minimal or robust IL-12 in vivo (Leishmania major or Listeria monocytogenes, respectively). Th1 cells developed under both conditions, and this was unaffected by the presence or absence of IFN-γ in non-T cells. Reconstitution with IFN-γ–deficient CD4+ T cells could not reestablish control over L. major, even in the presence of IFN-γ from the NK compartment. These data demonstrate that activated T cells can maintain responsiveness to IL-12 through elaboration of endogenous IFN-γ without requirement for an exogenous source of this cytokine.

scholarly journals The Lanostane Triterpenoids in Poria cocos Play Beneficial Roles in Immunoregulatory Activity

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 111
Author(s):  
Chien-Liang Chao ◽  
Hsin-Wen Huang ◽  
Muh-Hwan Su ◽  
Hang-Ching Lin ◽  
Wen-Mein Wu
Keyword(s):  
Immune Response ◽  
Interferon Γ ◽  
Th2 Cells ◽  
T Helper ◽  
Chinese Medicines ◽  
Poria Cocos ◽  
Ifn Γ ◽  
Preliminary Study

Poria cocos (Schwein) F.A. Wolf (syn. Wolfiporia cocos) dried sclerotium, called fuling, is an edible, saprophytic fungus commonly used as a tonic and anti-aging traditional Chinese medicine. It is traditionally used in combination with other traditional Chinese medicines to enhance immunity. This study showed that P. cocos extract (Lipucan®) containing lanostane triterpenoids has no immunotoxicity and enhances non-specific (innate) immunity though activating natural killer cells and promotes interferon γ (IFN-γ) secretion by Type 1 T-helper (Th1) cells immune response. In addition, P. cocos extract significantly decreased interleukin (IL-4 and IL-5) secretion by Type 2 T-helper (Th2) cells immune response, which are related to the allergy response. The purified lanostane triterpenoids were first identified as active ingredients of P. cocos with enhanced non-specific immunity by promoting interferon γ (IFN-γ) secretion in a preliminary study. Our findings support that the P. cocos extract plays beneficial roles in immunoregulatory activity.

scholarly journals Interdependency of Interleukin-10 and Interleukin-12 in Regulation of T-Cell Differentiation and Effector Function of Monocytes in Response to Stimulation withCryptococcus neoformans

2001 ◽  
Vol 69 (10) ◽  
pp. 6064-6073 ◽  
Author(s):  
Cinzia Retini ◽  
Thomas R. Kozel ◽  
Donatella Pietrella ◽  
Claudia Monari ◽  
Francesco Bistoni ◽  
...  
Keyword(s):  
T Cells ◽  
Critical Role ◽  
Principal Component ◽  
Interleukin 10 ◽  
Interleukin 12 ◽  
T Helper ◽  
Ifn Γ ◽  
Capsular Material ◽  
Type Response

ABSTRACT We previously demonstrated that the principal component of capsular material of Cryptococcus neoformans, glucuronoxylomannan (GXM), induces interleukin-10 (IL-10) secretion from human monocytes. Here we report that encapsulation of the yeast with GXM is able to down-regulate interleukin-12 (IL-12) production by monocytes that would normally occur in the absence of encapsulation. This phenomenon appeared to be the result of inhibition of the phagocytic process by encapsulation with GXM as well as of negative signals such as IL-10 secretion produced by interaction of GXM with leukocytes. Decreased secretion of IL-12 correlated with decreased release of gamma interferon (IFN-γ) from T cells, suggesting a role for encapsulation with GXM in hindering a T helper type 1 (Th1) response. This is supported by the ability of encapsulation with GXM to limit increased expression of B7-1 costimulatory molecules that otherwise might limit IL-10 secretion. Endogenous IL-10 played a critical role in modulatory activity associated with encapsulation with GXM. Blocking IL-10 with monoclonal antibody to IL-10 resulted in increased (i) IL-12 secretion, (ii) IFN-γ release from T cells, and (iii) killing of C. neoformans by monocytes. These results suggest that encapsulation with GXM limits development of a protective Th1-type response, an inhibitory process in which IL-10 plays a critical role. Scavengers of GXM and/or IL-10 could be useful in a protective Th1-type response in patients with cryptococcosis.

scholarly journals Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

2020 ◽  
Vol 8 (B) ◽  
pp. 738-746
Author(s):  
Haryudi Aji Cahyono ◽  
Wisnu Barlianto ◽  
Dian Handayani ◽  
Handono Kalim
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Premature Atherosclerosis ◽  
Ifn Γ ◽  
Tgf Β1

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process. AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]). METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019). RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%). CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

scholarly journals T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription

2006 ◽  
Vol 203 (3) ◽  
pp. 755-766 ◽  
Author(s):  
Takashi Usui ◽  
Jan C. Preiss ◽  
Yuka Kanno ◽  
Zheng Ju Yao ◽  
Jay H. Bream ◽  
...  
Keyword(s):  
Early Stage ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
Down Regulation ◽  
Ifng Gene ◽  
Deoxyribonuclease I ◽  
Negative Effect ◽  
Th2 Differentiation

T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3. Here we show that CD4+ cells from T-bet−/− mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti–interleukin (IL)-4 blockade of IL-4 receptor (R) signaling. In addition, under these conditions, Th1 cells from T-bet−/− mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity. In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet−/− cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed. Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels. These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rβ2 chain unless GATA-3 levels or function is regulated by T-bet. Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.

Effects of perioperative immunonutrition on cell-mediated immunity, T helper type 1 (Th1)/Th2 differentiation, and Th17 response after pancreaticoduodenectomy

Surgery ◽  
2010 ◽  
Vol 148 (3) ◽  
pp. 573-581 ◽  
Author(s):  
Daisuke Suzuki ◽  
Katsunori Furukawa ◽  
Fumio Kimura ◽  
Hiroaki Shimizu ◽  
Hiroyuki Yoshidome ◽  
...  
Keyword(s):  
Cell Mediated Immunity ◽  
T Helper ◽  
Th17 Response ◽  
Th2 Differentiation ◽  
Helper Type

scholarly journals Selective Expression and Functions of Interleukin 18 Receptor on T Helper (Th) Type 1 but not Th2 Cells

1998 ◽  
Vol 188 (8) ◽  
pp. 1485-1492 ◽  
Author(s):  
Damo Xu ◽  
Woon Ling Chan ◽  
Bernard P. Leung ◽  
David Hunter ◽  
Kerstin Schulz ◽  
...  
Keyword(s):  
Th2 Cells ◽  
Interleukin 18 ◽  
T Helper ◽  
Th2 Cell ◽  
A Cell ◽  
Ifn Γ

Interleukin (IL)-18 induces interferon (IFN)-γ synthesis and synergizes with IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells. IL-18R mRNA was expressed constitutively and consistently in long-term cultured clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the expression of IL-12Rβ2 mRNA, indicating that IL-18R transmits signals that maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated IL-18R mRNA. Antibody against an IL-18R–derived peptide bound Th1 but not Th2 clones. It also labeled polarized Th1 but not Th2 cells derived from naive ovalbumin–T cell antigen receptor-αβ transgenic mice (D011.10). Anti–IL-18R antibody inhibited IL-18– induced IFN-γ production by Th1 clones in vitro. In vivo, anti–IL-18R antibody reduced local inflammation and lipopolysaccharide-induced mortality in mice. This was accompanied by shifting the balance from Th1 to Th2 responses, manifest as decreased IFN-γ and proinflammatory cytokine production and increased IL-4 and IL-5 synthesis. Therefore, these data provide a direct mechanism for the selective effect of IL-18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12 and IL-18 on Th1 development may be due to the reciprocal upregulation of their receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from Th2 cells and may be a therapeutic target.

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