Txk, a Member of Nonreceptor Tyrosine Kinase of Tec Family, Acts as a Th1 Cell-Specific Transcription Factor and Regulates IFN-γ Gene Transcription

Takeba, Yuko; Nagafuchi, Hiroko; Takeno, Mitsuhiro; Kashiwakura, Jun‐ichi; Suzuki, Noboru

doi:10.4049/jimmunol.168.5.2365

Cited by 53 publications

(45 citation statements)

References 39 publications

(40 reference statements)

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“…Txk has been previously described as a Th1 cell-specific transcription factor, which regulates IFN-␥ gene transcription (45). Our Affymetrix data showed that its expression level was higher in Stat6-deficient cells compared with wt cells.…”

Section: And "#" (Differences Induced By Il-4 Comparing Wt and Stat6mentioning

confidence: 59%

Identification of Novel IL-4/Stat6-Regulated Genes in T Lymphocytes

Chen

Lund

Aittokallio

et al. 2003

The Journal of Immunology

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IL-4, primarily produced by T cells, mast cells, and basophiles, is a cytokine which has pleiotropic effects on the immune system. IL-4 induces T cells to differentiate to Th2 cells and activated B lymphocytes to proliferate and to synthesize IgE and IgG1. IL-4 is particularly important for the development and perpetuation of asthma and allergy. Stat6 is the protein activated by signal transduction through the IL-4R, and studies with knockout mice demonstrate that Stat6 is critical for a number of IL-4-mediated functions including Th2 development and production of IgE. In the present study, novel IL-4- and Stat6-regulated genes were discovered by using Stat6−/− mice and Affymetrix oligonucleotide arrays. Genes regulated by IL-4 were identified by comparing the gene expression profile of the wild-type T cells induced to polarize to the Th2 direction (CD3/CD28 activation + IL-4) to gene expression profile of the cells induced to proliferate (CD3/CD28 activation alone). Stat6-regulated genes were identified by comparing the cells isolated from the wild-type and Stat6−/− mice; in this experiment the cells were induced to differentiate to the Th2 direction (CD3/CD28 activation + IL-4). Our study demonstrates that a number a novel genes are regulated by IL-4 through Stat6-dependent and -independent pathways. Moreover, elucidation of kinetics of gene expression at early stages of cell differentiation reveals several genes regulated rapidly during the process, suggesting their importance for the differentiation process.

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Section: And "#" (Differences Induced By Il-4 Comparing Wt and Stat6mentioning

confidence: 59%

Identification of Novel IL-4/Stat6-Regulated Genes in T Lymphocytes

Chen

Lund

Aittokallio

et al. 2003

The Journal of Immunology

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“…A determining factor of CTL memory differentiation is the expression of IL-7R during the acute phase of infection (39). Genes like the Txk kinase and c-myb that are most commonly associated with thymocyte differentiation (40-42) may perhaps also act to facilitate T cell survival in the responding lymph nodes and spleen (42)(43)(44). Additional evidence for active transcriptional pathways in the splenic CD8 ϩ D b NP 366 ϩ set that could contribute to T cell survival comes from the identification of genes like pim1, which interacts with c-myb (45) and can enhance c-myb transcriptional activity (46).…”

Section: Discussionmentioning

confidence: 99%

Effector CD8⁺T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression

Marshall

Olivas

Andreansky

et al. 2005

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

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The restriction of influenza A virus replication to mouse respiratory epithelium means that this host response is anatomically compartmentalized, on the one hand, to sites of T cell stimulation and proliferation in the secondary lymphoid tissue and, on the other hand, to the site of effector T cell function and pathology in the pneumonic lung. Thus, it is hardly surprising that virus-specific CD8 ؉ T cells recovered by bronchoalveolar lavage (BAL) from the infected respiratory tract seem more ''activated'' in terms of both cytolytic activity and cytokine production than those cells isolated from the spleen. The present analysis uses Affymetrix microarray technology to compare profiles of gene expression in these two lineage-related, yet anatomically separate, lymphocyte populations. Ninety differentially expressed genes were identified for influenza-specific CD8 ؉ D b NP 366 ؉ T cells obtained directly ex vivo by BAL or spleen disruption, with nine genes being further analyzed by quantitative, real-time PCR at the population level. Integrin ␣E, for example, was shown by Affymetrix and real-time mRNA analyses and then by single-cell PCR and protein staining to be present at a much higher prevalence on the BAL CD8 ؉ D b NP366 ؉ set. The unpredicted finding, however, was that mRNA expression for 75% of the 90 genes was lower in T cells from the BAL than from the spleen. Apparently, the localization of virus-specific CD8 ؉ T cells to the site of virus-induced pathology is associated with a narrowing, or ''focusing,'' of gene expression that favors enhanced effector function in the damaged, ''high-antigen load'' environment of the pneumonic lung.Affymetrix gene array ͉ cytotoxic T cell ͉ influenza A virus ͉ viral immunology

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“…(31). The other Th1 transcription factor predominantly expressed at this time point is Txk, which has been shown to directly bind to the IFN-␥ promoter and activate its transcription (32). Txk is highly expressed in resting naïve CD4 ϩ T cells and down-regulated after TCR engagement.…”

Section: Clustering Analysis Revealed That Th1͞2 Differentiation Expementioning

confidence: 99%

Kinetic analysis of genomewide gene expression reveals molecule circuitries that control T cell activation and Th1/2 differentiation

Zagouras

Fischer

et al. 2004

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

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The global gene expression profiling of early T helper (Th) 1 and Th2 differentiation reveals that this process can be divided into two stages, activation and differentiation. The activation stage is manifested in coordinated mobilization of the replication machinery, a process that we hypothesize may be responsible for establishing genomewide opening of transcription loci. The molecular programs underlying the differentiation stage consist of highly regulated expression of functional groups of genes that are important for the biological properties of Th1͞2 cells and transcription factors that are likely important in establishing terminal differentiation of these cells. The kinetics of expression pattern of a number of transcription factors shed new light on the molecular events that shape the outcome of Th1͞2 differentiation.

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Txk, a Member of Nonreceptor Tyrosine Kinase of Tec Family, Acts as a Th1 Cell-Specific Transcription Factor and Regulates IFN-γ Gene Transcription

Cited by 53 publications

References 39 publications

Identification of Novel IL-4/Stat6-Regulated Genes in T Lymphocytes

Identification of Novel IL-4/Stat6-Regulated Genes in T Lymphocytes

Effector CD8⁺T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression

Kinetic analysis of genomewide gene expression reveals molecule circuitries that control T cell activation and Th1/2 differentiation

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Txk, a Member of Nonreceptor Tyrosine Kinase of Tec Family, Acts as a Th1 Cell-Specific Transcription Factor and Regulates IFN-γ Gene Transcription

Cited by 53 publications

References 39 publications

Identification of Novel IL-4/Stat6-Regulated Genes in T Lymphocytes

Identification of Novel IL-4/Stat6-Regulated Genes in T Lymphocytes

Effector CD8+T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression

Kinetic analysis of genomewide gene expression reveals molecule circuitries that control T cell activation and Th1/2 differentiation

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Effector CD8⁺T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression