CD28 Costimulation Controls Histone Hyperacetylation of the Interleukin 5 Gene Locus in Developing Th2 Cells

Inami, Masamichi; Yamashita, Masakatsu; Tenda, Yoshiyuki; Hasegawa, Akira; Kimura, Motoko; Hashimoto, Kimio; Seki, Nobuo; Taniguchi, Masaru; Nakayama, Toshinori

doi:10.1074/jbc.m401248200

Cited by 39 publications

(42 citation statements)

References 61 publications

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“…ROG was originally reported to be a repressor of GATA3-induced transactivation of the IL-4 and IL-5 promoters in the M12 B and EL-4 T cell lines by preventing GATA3 from binding to DNA (37). GATA3 is required for chromatin remodeling of the IL-4 and IL-13 gene loci (24) and the IL-5 gene locus (38). The levels of transcription of the IL-5 and IL-13 genes are highly dependent on GATA3.…”

Section: Discussionmentioning

confidence: 99%

STAT6-Dependent Differentiation and Production of IL-5 and IL-13 in Murine NK2 Cells

Katsumoto

Kimura

Yamashita

et al. 2004

The Journal of Immunology

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NK cells differentiate into either NK1 or NK2 cells that produce IFN-γ or IL-5 and IL-13, respectively. Little is known, however, about the molecular mechanisms that control NK1 and NK2 cell differentiation. To address these questions, we established an in vitro mouse NK1/NK2 cell differentiation culture system. For NK1/NK2 cell differentiation, initial stimulation with PMA and ionomycin was required. The in vitro differentiated NK2 cells produced IL-5 and IL-13, but the levels were 20 times lower than those of Th2 or T cytotoxic (Tc)2 cells. No detectable IL-4 was produced. Freshly prepared NK cells express IL-2Rβ, IL-2RγC, and IL-4Rα. After stimulation with PMA and ionomycin, NK cells expressed IL-2Rα. NK1 cells displayed higher cytotoxic activity against Yac-1 target cells. The levels of GATA3 protein in developing NK2 cells were approximately one-sixth of those in Th2 cells. Both NK1 and NK2 cells expressed large amounts of repressor of GATA, the levels of which were equivalent to CD8 Tc1 and Tc2 cells and significantly higher than those in Th2 cells. The levels of histone hyperacetylation of the IL-4 and IL-13 gene loci in NK2 cells were very low and equivalent to those in naive CD4 T cells. The production of IL-5 and IL-13 in NK2 cells was found to be STAT6 dependent. Thus, similar to Th2 cells, NK2 cell development is dependent on STAT6, and the low level expression of GATA3 and the high level expression of repressor of GATA may influence the unique type 2 cytokine production profiles of NK2 cells.

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Section: Discussionmentioning

confidence: 99%

STAT6-Dependent Differentiation and Production of IL-5 and IL-13 in Murine NK2 Cells

Katsumoto

Kimura

Yamashita

et al. 2004

The Journal of Immunology

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“…27 In addition, NF-kB is required for CD28-triggered hyperacetylation of histones H3 and H4 at the IL-5 gene locus. 28 It will be interesting to learn whether the reported CD28-mediated loss of cytosine methylation and increase in histone acetylation 29 also involve the participation of NF-kB family members and what cellular pathways mediate CD28-triggered and NF-kBdependent chromatin remodelling.…”

Section: The Concept Of T Cell Costimulationmentioning

confidence: 99%

Controlling NF-κB activation in T cells by costimulatory receptors

Schmitz

Krappmann

2006

Cell Death Differ

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Full and productive activation of T lymphocytes relies on the simultaneous delivery of T cell receptor (TCR)-and coreceptor-derived signals. In naïve T cells engagement of the TCR alone causes anergy, while TCR triggering of preactivated T cells results in activation-induced cell death. Costimulatory signals are prominently mirrored by the activation of NF-kB, which needs input from the TCR as well as from coreceptors in order to be fully activated and to fulfil its crucial function in the immune response. Coreceptorgenerated signals tightly control the duration and amplitude of the NF-kB response. The activation of IkB kinase (IKK) complex at the contact zone between a T cell and an antigenpresenting cell offers the unique opportunity to study the spatial organization of IKK activation. Recent studies indicate that coreceptor pathways influence the threshold activities of many signalling mediators and thus act on multiple layers of the NF-kB pathway.

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“…The hyperacetylation of histones associated with the Th2 cytokine gene locus is dependent on the expression of GATA3 (43,46). Activation of the ERK-MAPK cascade is required for GATA3-dependent histone H3 hyperacetylation of the Th2 cytokine gene locus (16).…”

Section: Chromatin Remodeling Of the Th2 Cytokine Gene Locus In Cd4 ϩmentioning

confidence: 99%

“…The productions of IL-2, IL-4, IL-5, IL-13, and IFN-␥ were measured by ELISA as described previously (43).…”

Section: Elisa For the Measurement Of Cytokine Concentrationmentioning

confidence: 99%

Impaired GATA3-Dependent Chromatin Remodeling and Th2 Cell Differentiation Leading to Attenuated Allergic Airway Inflammation in Aging Mice

Hasegawa

Miki

Hosokawa

et al. 2006

The Journal of Immunology

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Age-related changes in lymphocytes are most prominent in the T cell compartment. There have been substantial numbers of reports on T cell function in aged mice and humans, such as on the production of Th1 and Th2 cytokines, but the results show considerable variation and contradictions. In the present study, we used 8- to 12-mo-old aging mice and a well-established in vitro Th1/Th2 cell differentiation culture system to identify molecular defects in Th1/Th2 cell differentiation that can be detected in the relatively early stages of aging. The capability to differentiate into Th2 cells is reduced in aging mouse CD4+ T cells. Decreased activation of the ERK MAPK cascade upon TCR stimulation, but normal intracellular-free calcium ion concentration mobilization and normal IL-4-induced STAT6 activation were observed in aging mouse CD4+ T cells. In addition, reduced expression of GATA3 was detected in developing Th2 cells. Chromatin remodeling of the Th2 cytokine gene locus was found to be impaired. Th2-dependent allergic airway inflammation was milder in aging mice compared with in young adult mice. These results suggest that the levels of Th2 cell differentiation and resulting Th2-dependent immune responses, including allergic airway inflammation, decline during aging through defects in the activation of the ERK MAPK cascade, expression of GATA3 protein and GATA3-dependent chromatin remodeling of the Th2 cytokine gene locus. In the present study, we provide the first evidence indicating that a chromatin-remodeling event in T cells is impaired by aging.

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CD28 Costimulation Controls Histone Hyperacetylation of the Interleukin 5 Gene Locus in Developing Th2 Cells

Cited by 39 publications

References 61 publications

STAT6-Dependent Differentiation and Production of IL-5 and IL-13 in Murine NK2 Cells

STAT6-Dependent Differentiation and Production of IL-5 and IL-13 in Murine NK2 Cells

Controlling NF-κB activation in T cells by costimulatory receptors

Impaired GATA3-Dependent Chromatin Remodeling and Th2 Cell Differentiation Leading to Attenuated Allergic Airway Inflammation in Aging Mice

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