Suppressive role of C-terminal binding protein 1 in IL-4 synthesis in human T cells

Kitamura, Noriko; Motoi, Yuji; Mori, Akio; Tatsumi, Hideki; Nemoto, Soichi; Miyoshi, Hiroyuki; Kitamura, Fujiko; Miyatake, Shoichiro; Hiroi, Takachika; Kaminuma, Osamu

doi:10.1016/j.bbrc.2009.03.017

Cited by 5 publications

(6 citation statements)

References 31 publications

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“…This cell type transcribes IL-4 as well as IFN-γ upon stimulation, whereas it does not release proteins or express counter receptors of these cytokines; therefore, it enables separation from the overall effects on Th1/Th2 subset differentiation. Consistent with previous reports [11,12], the transcriptional activity of the IL-4 and IFN-γ promoters encompassing –1105 to +4 and –346 to +7, respectively, was enhanced upon stimulation (fig. 2).…”

Section: Resultssupporting

confidence: 81%

“…In addition, ZFPM1-mediated suppression of GATA activity was diminished by mutation in this motif [17]. Since we have recently demonstrated that CtBP indeed suppresses Th2 cytokine synthesis in human T cells [12,18], further investigations will be required in order to elucidate additional details of the functional contribution of the GATA-3/ZFPM1/CtBP-related transcription pathway to IL-4 synthesis in human CD4+ T cells.…”

Section: Resultsmentioning

confidence: 99%

“…Venus, at the C-terminal end [9,10], as well as in the pEF6/His vector (Invitrogen, Carlsbad, Calif., USA) (pEF-ZFPM1). The promoter reporter vectors for the human IL-4 and IFN -γ genes (IL-4-LUC and IFN-γ-LUC) were described [11,12]. The correct sequences of all constructs were verified by sequencing.…”

Section: Methodsmentioning

confidence: 99%

“…After 24 h of transfection, cells were stimulated with PMA plus ionomycin for 16 h and then harvested, washed, and lysed. Luciferase activity in the cells was determined and expressed as arbitrary units normalized to pTK-EGFP activity assessed as the fluorescence of synthetic EGFP as described previously [11,12]. …”

Section: Methodsmentioning

confidence: 99%

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Zinc Finger Protein, Multitype 1, Suppresses Human Th2 Development via Downregulation of IL-4

Kitamura

Mori²,

Tatsumi³

et al. 2011

Int Arch Allergy Immunol

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Background: Among several GATA family transcription factor-associating proteins, zinc finger protein, multitype 1 (ZFPM1), at least that of murine origin, has been shown to modulate the activity of GATA-3. However, the functional role of human ZFPM1 in the immune system has not been elucidated. Therefore, we here investigated the contribution of ZFPM1 to human Th1/Th2 differentiation. Methods: The cDNA of ZFPM1 was cloned and introduced into human cord blood CD4+ T cells by a lentiviral transduction system. Then, the expression of IL-4 and IFN-γ mRNA was determined by quantitative real-time RT-PCR. The effect of ZFPM1 on the promoter activity of IL-4 and IFN-γ in Jurkat cells was also investigated. Results: Stimulation-induced expression of IL-4 and IFN-γ in human CD4+ T cells was suppressed and enhanced, respectively, by the introduction of ZFPM1. The transcriptional activity of IL-4 was also diminished by ZFPM1, whereas that of IFN-γ was not affected. Conclusion: ZFPM1 that facilitates human Th1 differentiation via the downregulation of IL-4 is a potential target for the treatment of allergic diseases.

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Zinc Finger Protein, Multitype 1, Suppresses Human Th2 Development via Downregulation of IL-4

Kitamura

Mori²,

Tatsumi³

et al. 2011

Int Arch Allergy Immunol

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“…Others have identified IL‐2 as a putative physiological target for FOXP1 via its direct binding to FOXP consensus DNA‐binding sites present in the IL‐2 promoter . IL‐4 expression, a cytokine critical for Th2 polarization, may also be regulated by FOXP1 both through its inhibitory effects on GATA3 and its interactions with CtBP‐1, which is important for human Th1/Th2 differentiation due to its selective downregulation of IL‐4 synthesis . Further studies are needed to assess whether FOXP1 indirectly regulates expression of the spectrum of cytokines that are overproduced in L‐HES, before hypothesizing that FOXP1 repression is involved in the,marked hypereosinophilia and elevated IgE levels that characterize this disease .…”

Section: Discussionmentioning

confidence: 99%

FOXP1 is a regulator of quiescence in healthy human CD4⁺ T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders

et al. 2016

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The forkhead box P1 (FOXP1) transcription factor has been shown to regulate the generation and maintenance of quiescent naïve murine T cells. In humans, FOXP1 expression has been correlated with overall survival in patients with peripheral T-cell lymphoma (PTCL), although its regulatory role in T-cell function is currently unknown. We found that FOXP1 is normally expressed in all human leukocyte subpopulations. Eur. J. Immunol. 2017. 47: 168-179 Immunomodulation and immune therapies 169 IntroductionCellular quiescence defines cell cycle arrest in the G0 phase, which is characterized by lower rates of transcription, translation, and metabolism thereby reducing the consumption of nutrients required to maintain cellular activities. This reversible state may indirectly deter malignant transformation by protecting cells from metabolic damage. In lymphocytes, quiescence is distinct from anergy and senescence and can be reversed by antigenic stimulation. Initially, quiescence was thought to result from the absence of activating signals, but growing evidence from murine models and in vitro cell line studies reveals that quiescence is actively controlled by a transcriptional program [1]. Several transcription factors (TF) have been shown to play a role in T-cell quiescence, including LKLF, a zinc finger TF and TOB1, an anti-proliferative TF [2,3]. Expression levels of these transcriptional regulators are high in naïve T cells and decrease dramatically following TCR crosslinking. Their suppression decreases the T-cell activation threshold, resulting in increased T-cell proliferation and effector functions. Murine studies have shown that a forkhead box (FOX) TF, FOXP1, is essential for the generation of quiescent naïve T cells during thymocyte development and maintaining quiescence in the periphery [4,5].The FOX TF family performs diverse functions, including regulating development and organogenesis, metabolism, and immune responses. FOX TF are identified by a conserved 110-amino acid DNA-binding (winged helix) domain [6,7]. Members of the FOXP subfamily, including FOXP1-FOXP4, contain a zinc finger domain and a leucine zipper motif and form homo-or heterodimers [8]. In the murine immune system, FOXP1 acts as an essential transcriptional regulator of B-cell lymphopoiesis by directly regulating the B-cell specific Erag enhancer [9]. Moreover, its downregulation is required for B-cell transit through the germinal center (GC) [10]. FOXP1 is also expressed in monocytes and has been shown to regulate their differentiation both in human cell lines and in a murine model where it was also shown to control macrophage functions [11,12]. A recent study demonstrated that upregulation of FOXP1 in CD8 + T cells drives T-cell unresponsiveness in cancer by blocking proliferation and major T cell functions, including degranulation of cytotoxic granules and cytokine release. This state, which is distinct from anergy and exhaustion, involves FOXP1 and Smad2/Smad3 interactions, both translocated to the nucleus in response to TGF-β signalin...

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Marek’s Disease Virus-Induced T-Cell Lymphomas

Parcells

Burnside

Morgan

2011

Cancer Associated Viruses

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Suppressive role of C-terminal binding protein 1 in IL-4 synthesis in human T cells

Cited by 5 publications

References 31 publications

Zinc Finger Protein, Multitype 1, Suppresses Human Th2 Development via Downregulation of IL-4

Zinc Finger Protein, Multitype 1, Suppresses Human Th2 Development via Downregulation of IL-4

FOXP1 is a regulator of quiescence in healthy human CD4⁺ T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders

Marek’s Disease Virus-Induced T-Cell Lymphomas

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Suppressive role of C-terminal binding protein 1 in IL-4 synthesis in human T cells

Cited by 5 publications

References 31 publications

Zinc Finger Protein, Multitype 1, Suppresses Human Th2 Development via Downregulation of IL-4

Zinc Finger Protein, Multitype 1, Suppresses Human Th2 Development via Downregulation of IL-4

FOXP1 is a regulator of quiescence in healthy human CD4+ T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders

Marek’s Disease Virus-Induced T-Cell Lymphomas

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FOXP1 is a regulator of quiescence in healthy human CD4⁺ T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders