Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression

Rengarajan, Jyothi; Mowen, Kerri; McBride, Kathryn D.; Smith, Erica D.; Singh, Harinder; Glimcher, Laurie H.

doi:10.1084/jem.20011128

Cited by 301 publications

(266 citation statements)

References 30 publications

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“…IRF-8 directs the expression of IL-12 (49) and IL-18 (50), promoting Th1-biased immune responses. On the other hand, IRF-4 is involved in the Th2-bias, by promoting IL-4 production by CD4 ϩ T-cells and regulating their responsiveness to IL-4 (24,51,52). Therefore, it is intriguing to speculate that the IRF-4 expressed The wild-type and IRF-4 Ϫ/Ϫ DCs were stained with anti-CD11b-biotin and anti-CD11c-PE, followed by intracellular staining as described in A.…”

Section: Discussionmentioning

confidence: 99%

Critical roles of interferon regulatory factor 4 in CD11b^highCD8α^–dendritic cell development

Suzuki

Honma

Matsuyama

et al. 2004

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

281

200

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Section: Discussionmentioning

confidence: 99%

Critical roles of interferon regulatory factor 4 in CD11b^highCD8α^–dendritic cell development

Suzuki

Honma

Matsuyama

et al. 2004

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

281

200

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“…In the nucleus, NFAT family members associate with other nuclear transcription factors (e.g. JUN, GATA4, IRF, C/EBP) depending on the cell type, to mediate transcription of specific genes including cytokine and cytokine receptor genes [15][16][17]. In addition to the regulation of their nuclear localisation by phosphorylation/dephosphorylation, NFAT members can also be regulated at the level of gene expression.…”

Section: Introductionmentioning

confidence: 99%

Nuclear factor of activated T (NFAT) cells activity within CD4+ T cells is influenced by activation status and tissue localisation

Harris¹,

Watt²,

MacLenachan³

et al. 2006

Microbes and Infection

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Nuclear factor of activated T (NFAT) cells is a family of transcription factors important for the regulation of cytokine expression by CD4+ T cells. Whilst a number of studies have examined NFAT activity of in vitro generated CD4+ T helper (Th)1 and Th2 cells, regulation of NFAT during in vivo immune responses has yet to be elucidated. We show that NFAT activity in CD4+ T cells peaked at early time-points in the draining mediastinal lymph node of mice infected with influenza A (Flu) or Nippostrongylus brasiliensis (Nb). In contrast, low NFAT transcriptional activity was detected in CD4+ T cells isolated from the lung of either Flu or Nb infected mice, despite a greater proportion of cytokine-producing cells being present at this site. These findings indicate that the activation status and tissue microenvironment of effector CD4+ T cells can determine their requirement for NFAT-mediated transcription.

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“…It remains to be determined whether PU.1/Spi-B regulate Ig light-chain gene expression during the pre-B-to-B transition. IRF-4 −/− mutant mice exhibit profound defects in B-and T-cell activation that are manifested in the failure to mount antibody, cytotoxic, or antitumor responses (Mittrucker et al 1997;Rengarajan et al 2002). IRF-8 −/− mutant mice are impaired in macrophage development, highly susceptible to viral infections, and manifest a chronic myelogenous leukemia-like syndrome (Holtschke et al 1996).…”

mentioning

confidence: 99%

IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development

Lu¹,

Medina²,

Lancki³

et al. 2003

Genes Dev.

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IRF-4,8 are two specialized members of the interferon regulatory factor (IRF) family that have been implicated in regulating immunoglobulin (Ig) light-chain gene transcription during B-lymphocyte development (Pongubala et al. 1992;Eisenbeis et al. 1995;Shaffer et al. 1997;Brass et al. 1999; Muljo and Schlissel 2002). They are more highly related to one another than to other IRFs and are selectively expressed in the lymphoid and myeloid lineages of the immune system (for review, see Taniguchi et al. 2001). IRF-4,8 bind very weakly to DNA-containing IRF sites, but are recruited to their binding sites via interactions with other transcription factors. In particular, the related Ets family transcription factors PU.1 and Spi-B have been shown to recruit IRF-4 or IRF-8 to Ets-IRF composite elements (EICE) in Ig 3Ј and enhancers (Pongubala et al. 1992;Eisenbeis et al. 1995;Brass et al. 1999;Escalante et al. 2002). These heterodimeric protein complexes have been implicated in the control of Ig light-chain gene transcription. PU.1 is required for early B-cell development and Spi-B is important for B-cell activation (Scott et al. 1994;Su et al. 1997). It remains to be determined whether PU.1/Spi-B regulate Ig light-chain gene expression during the pre-B-to-B transition. IRF-4 −/− mutant mice exhibit profound defects in B-and T-cell activation that are manifested in the failure to mount antibody, cytotoxic, or antitumor responses (Mittrucker et al. 1997;Rengarajan et al. 2002). IRF-8 −/− mutant mice are impaired in macrophage development, highly susceptible to viral infections, and manifest a chronic myelogenous leukemia-like syndrome (Holtschke et al. 1996). Loss of either IRF-4 or IRF-8 does not block the generation of B lymphocytes. Given their structural relatedness and similar molecular properties, we sought to examine whether they function redundantly to regulate Ig lightchain gene expression and the pre-B-to-B transition. (Fig. 1A). Strikingly, the double mutant mice lacked sIgM + peripheral B lymphocytes (Fig. 1B). In contrast, splenic T lymphocytes, (CD4 + or CD8 + ) were present in the double mutant mice, albeit with reduced numbers (Fig. 1C). We note that loss of IRF-4 and IRF-8 does not impair T-cell development in the thymus (data not shown). We next examined B-cell generation in the bone marrow. Immature IgM + B cells were absent in the IRF-4,8 −/− bone marrow (Fig. 1D). These results establish that the combined loss of IRF-4,8 causes a lineage-specific block to B-cell development. It should be noted that as is the case for IRF-8 −/− mice, there was an increase in the numbers of myeloid cells Fig. 2A). The levels of HSA expression on the mutant B220 + , CD43 + , BP-1 + , B-lineage cells were particularly high, suggesting that they represent transitional pre-B cells, which are a subset of fraction C cells in the nomenclature of Hardy et al. (1991). The disproportionate increase in the percentage fraction C cells in the IRF-4,8 −/− bone marrow ( Fig. 2A) was also reflected in a substantial increase in their a...

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Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression

Cited by 301 publications

References 30 publications

Critical roles of interferon regulatory factor 4 in CD11b^highCD8α^–dendritic cell development

Critical roles of interferon regulatory factor 4 in CD11b^highCD8α^–dendritic cell development

Nuclear factor of activated T (NFAT) cells activity within CD4+ T cells is influenced by activation status and tissue localisation

IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development

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Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression

Cited by 301 publications

References 30 publications

Critical roles of interferon regulatory factor 4 in CD11bhighCD8α–dendritic cell development

Critical roles of interferon regulatory factor 4 in CD11bhighCD8α–dendritic cell development

Nuclear factor of activated T (NFAT) cells activity within CD4+ T cells is influenced by activation status and tissue localisation

IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development

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Critical roles of interferon regulatory factor 4 in CD11b^highCD8α^–dendritic cell development

Critical roles of interferon regulatory factor 4 in CD11b^highCD8α^–dendritic cell development