Eomesodermin Controls Interleukin-5 Production in Memory T Helper 2 Cells through Inhibition of Activity of the Transcription Factor GATA3

Endo, Yusuke; Iwamura, Chiaki; Kuwahara, Makoto; Suzuki, Akane; Sugaya, Kimio; Tumes, Damon J.; Tokoyoda, Koji; Hosokawa, Hiroyuki; Yamashita, Masakatsu; Nakayama, Toshinori

doi:10.1016/j.immuni.2011.08.017

Cited by 104 publications

(122 citation statements)

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“…A previous report identified Eomes expression in a small population of nonconventional intestinal intraepithelial Th1 CD4 + T lymphocytes with an activated phenotype (40). Eomes was also shown to be expressed by a subset of memory T lymphocytes generated after adoptive transfer of Th2 cells into a nude host (10). More generally, a significant CD4 + Eomes + population has been described during systemic 4-1BB-mediated stimulation (11,57,58).…”

Section: Discussionmentioning

confidence: 84%

“…Among these, the T-bet paralogue eomesodermin (Eomes) has been shown to affect Th polarization (8)(9)(10)(11). Eomes is a T-box transcription factor initially described as a crucial player in embryonic development, and Eomes-deficient mice die early during embryonic development (12,13).…”

Section: T He Cd4 + T Cells Coordinate Different Types Of Immunementioning

confidence: 99%

“…In contrast, different experimental studies suggest that, like T-bet, Eomes is able to actively suppress the development or function of non-Th1 CD4 + subsets. T-bet and Eomes have been described to interact directly with GATA3 in a subset of Th2 memory cells, sequestering it away from the Il5 promoter and blocking IL-5 production (10,25). Eomes overexpression can also suppress Th17 differentiation by directly blocking transcription at both Rorc and Il17a loci (26).…”

Section: T He Cd4 + T Cells Coordinate Different Types Of Immunementioning

confidence: 99%

See 2 more Smart Citations

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Lupar¹,

Brack

Garnier

et al. 2015

The Journal of Immunology

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CD4+ T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3+ regulatory T cell fates, the role of the T-bet–related transcription factor eomesodermin (Eomes) in CD4+ T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4+ T lymphocytes. We find that Eomes is readily expressed in activated CD4+ Th1 T cells in vivo. Eomes+ CD4+ T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4+ T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3+ cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4+ T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4+ T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4+ T cells. This enhanced capacity of Eomes-deficient CD4+ T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3+ cells. Our data identify a novel role for Eomes in CD4+ T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis.

show abstract

Section: Discussionmentioning

confidence: 84%

Section: T He Cd4 + T Cells Coordinate Different Types Of Immunementioning

confidence: 99%

Section: T He Cd4 + T Cells Coordinate Different Types Of Immunementioning

confidence: 99%

See 1 more Smart Citation

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Lupar¹,

Brack

Garnier

et al. 2015

The Journal of Immunology

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“…Previously identified Gata3-regulators such as repressor of GATA (Rog), Fog, spleen focus forming virus proviral integration oncogene spi1 (PU.1), T-bet, lymphoid enhancer factor 1 (Lef1), Eomesodermin, and Sox4 appear to primarily regulate Gata3 through inhibition of its DNA binding (27)(28)(29)(30)(31)(32)(33). However, in this study we show that the Gata3/Chd4-NuRD complex mediated direct repression of transcription through chromatin modulation of the Gata3 target gene regulatory regions (Fig.…”

Section: Discussionmentioning

confidence: 99%

Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity

Hosokawa¹,

Tanaka

Suzuki

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naïve CD4 T cells into T helper 2 (Th2) cells. However, it is unknown how Gata3 simultaneously activates Th2-specific genes while repressing those of other Th lineages. Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFN-γ. We define a Gata3/Chd4/p300 transcriptional activation complex at the Th2 cytokine loci and a Gata3/Chd4–nucleosome remodeling histone deacetylase repression complex at the Tbx21 locus in Th2 cells. We also demonstrate a physiological role for Chd4 in Th2-dependent inflammation in an in vivo model of asthmatic inflammation. Thus, Gata3/Chd4 forms functionally distinct complexes, which mediate both positive and negative gene regulation to facilitate Th2 cell differentiation.

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“…On the other hand, memory CD4 T cells induce or prolong inflammatory diseases, such as allergic disorders (3,4) and autoimmune diseases (5). After antigen recognition by the T-cell receptor (TCR), naïve CD4 T cells undergo clonal expansion and become functionally polarized effector T helper (Th) cells (e.g., Th1, Th2, and Th17 cells) within 1 or 2 wk (6, 7).…”

mentioning

confidence: 99%

Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo

Iwamura

Shinoda

Endo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms of immunological memory. Factors regulating memory CD4 + T helper (Th)-cell pool size and function remain unclear, however. We show that activation of type I invariant natural killer T (iNKT) cells with glycolipid ligands and activation of type II natural killer T (NKT) cells with the endogenous ligand sulfatide induced dramatic proliferation and expansion of memory, but not naïve, CD4 T cells. NKT cell-induced proliferation of memory Th1 and Th2 cells was dependent largely on the production of IL-2, with Th2-cell proliferation also affected by loss of IL-4. Type II NKT cells were also required for efficient maintenance of memory CD4 T cells in vivo. Activation of iNKT cells resulted in up-regulation of IFN-γ expression by memory Th2 cells. These IFN-γ-producing memory Th2 cells showed a decreased capability to induce Th2 cytokines and eosinophilic airway inflammation. Thus, activated NKT cells directly regulate memory CD4 T-cell pool size and function via the production of cytokines in vivo.α-galactosylceramide | CD1d KO mice | Jα18 KO mice | STAT5 | allergy

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Eomesodermin Controls Interleukin-5 Production in Memory T Helper 2 Cells through Inhibition of Activity of the Transcription Factor GATA3

Cited by 104 publications

References 48 publications

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction

Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity

Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo

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