A Novel Role for the Major Histocompatibility Complex Class II Transactivator CIITA in the Repression of IL-4 Production

Gourley, Tania; Roys, Stacey; Lukacs, Nicholas W.; Kunkel, Steven L.; Flavell, Richard A.; Chang, Cheong Hee

doi:10.1016/s1074-7613(00)80037-0

Cited by 76 publications

(128 citation statements)

References 67 publications

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“…This suggests that CIITA is highly dedicated to the regulation of MHC-II expression. Nevertheless, a series of reports have implicated CIITA in the regulation of a wide variety of other genes functioning within and outside the immune system [8][9][10][11][12][13][14]20]. These reports suggested that CIITA might play a pleiotropic role in various biological processes.…”

Section: Discussionmentioning

confidence: 99%

“…Several reports have established that deregulated CIITA expression has an impact on cytokine gene activation during Th1/Th2 differentiation [8,15,16,18]. Th1 cells from CIITA-deficient mice were found to exhibit de-repressed IL-4 expression [8,23].…”

Section: Discussionmentioning

confidence: 99%

“…The genes encoding IL-4 and Fas ligand (FasL) were proposed to be repressed by CIITA in mouse T cells [8,9]. Those encoding cathepsin E and IL-10 were suggested to be repressed by CIITA in mouse B cells and/or DC [10,11].…”

Section: Molecular Immunologymentioning

confidence: 99%

“…Deregulated cytokine expression in CIITA-Tg CD4 + T cells CIITA has been shown to modulate expression of the genes encoding IL-4 and IFN-c in activated mouse Th cells [8,15,16,18]. However, this influence of CIITA on cytokine production and the mechanisms that are responsible have been a matter of debate [8,15,16,18,[21][22][23].…”

Section: Impact Of Ciita On New Candidate Target Genesmentioning

confidence: 99%

“…However, this influence of CIITA on cytokine production and the mechanisms that are responsible have been a matter of debate [8,15,16,18,[21][22][23]. We therefore addressed this question further using our Tg mice.…”

Section: Impact Of Ciita On New Candidate Target Genesmentioning

confidence: 99%

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Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Otten¹,

LeibundGut‐Landmann²,

Huarte³

et al. 2006

Eur J Immunol

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CIITA is a master regulatory factor for the expression of MHC class II (MHC-II) and accessory genes involved in Ag presentation. It has recently been suggested that CIITA also regulates numerous other genes having diverse functions within and outside the immune system. To determine whether these genes are indeed relevant targets of CIITA in vivo, we studied their expression in CIITA-transgenic and CIITA-deficient mice. In contrast to the decisive control of MHC-II and related genes by CIITA, nine putative non-MHC target genes (Eif3s2, Kpna6, Tap1, Yars, Col1a2, Ctse, Ptprr, Tnfsf6 and Plxna1) were found to be CIITA independent in all cell types examined. Two other target genes, encoding IL-4 and IFN-c, were indeed found to be up-and down-regulated, respectively, in CIITA-transgenic CD4 + T cells. However, there was no correlation between MHC-II expression and this Th2 bias at the level of individual transgenic T cells, indicating an indirect control by CIITA. These results show that MHC-II-restricted Ag presentation, and its indirect influences on T cells, remains the only pathway under direct control by CIITA in vivo. They also imply that precisely regulated MHC-II expression is essential for maintaining a proper Th1-Th2 balance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Molecular Immunologymentioning

confidence: 99%

Section: Impact Of Ciita On New Candidate Target Genesmentioning

confidence: 99%

Section: Impact Of Ciita On New Candidate Target Genesmentioning

confidence: 99%

See 3 more Smart Citations

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Otten¹,

LeibundGut‐Landmann²,

Huarte³

et al. 2006

Eur J Immunol

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Mini‐review: Specificity and expression of CIITA, the master regulator of MHC class II genes

et al. 2004

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The class II transactivator (CIITA) has been referred to as the "master control factor" for the expression of MHC class II (MHCII) genes. As our knowledge on the specificity and function of CIITA grows, it is becoming increasingly evident that this sobriquet is entirely justified. First, despite extensive investigations, the major target genes of CIITA remain those implicated in the presentation of antigenic peptides by MHCII molecules. Although other putative target genes have been reported, the contribution of CIITA to their expression remains indirect, controversial or comparatively minor relative to its decisive role as a regulator of MHCII and related genes. Second, the most important parameter dictating MHCII expression is by far the expression pattern of the gene encoding CIITA (MHC2TA). The vast majority of signals that activate or repress MHCII expression under physiological and pathological situations converge on one or more of the three alternative promoters that drive transcription of the MHC2TA gene. In short, with respect to its specificity and its exquisitely controlled pattern of expression, CIITA is by a long stretch the single most important transcription factor for the regulation of genes required for MHCII-restricted antigen-presentation.

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Revisiting the specificity of the MHC class II transactivator CIITA in classical murine dendritic cells in vivo

et al. 2017

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Ciita was discovered for its role in regulating transcription of major histocompatibility complex class II (MHCII) genes. Subsequently, CIITA was predicted to control many other genes based on reporter and ChIP-seq analysis but few such predictions have been verified in vivo using Ciita−/− mice. Testing these predictions for classical dendritic cells (cDCs) has been particularly difficult, since Ciita−/− mice lack MHCII expression required to identify cDCs. However, recent identification of the cDC-specific transcription factor Zbtb46 allows identification of cDCs independently of MHCII expression. We crossed Zbtb46gfp mice onto the Ciita−/− background and found that all cDC lineages developed in vivo in the absence of Ciita. We then compared the complete transcriptional profile of wild-type and Ciita−/− cDCs to define the physiological footprint of CIITA for both immature and activated cDCs. We find that CIITA exerts a highly restricted control over only the MHCII, H2-DO and H2-DM genes, in DC1 and DC2 cDC subsets, but not over other proposed targets, including Ii. These findings emphasize the caveats needed in interpreting transcription factor binding sites identified by in vitro reporter analysis, or by ChIP-seq, which may not necessarily indicate their functional activity in vivo.

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A Novel Role for the Major Histocompatibility Complex Class II Transactivator CIITA in the Repression of IL-4 Production

Cited by 76 publications

References 67 publications

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Revisiting the specificity of the MHC class II transactivator CIITA in vivo

Mini‐review: Specificity and expression of CIITA, the master regulator of MHC class II genes

Revisiting the specificity of the MHC class II transactivator CIITA in classical murine dendritic cells in vivo

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