Mice Lacking the MHC Class II Transactivator (CIITA) Show Tissue-Specific Impairment of MHC Class II Expression

Chang, Cheong Hee; Guerder, Sylvie; Hong, Soon Cheol; Ewijk, Willem van; Flavell, Richard A.

doi:10.1016/s1074-7613(00)80681-0

Cited by 334 publications

(304 citation statements)

References 47 publications

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“…Particularly convincing support was provided by the fact that MHC-II expression is abolished in CIITA-deficient BLS patients and CIITA knockout mice [2,3,19,25,26]. In both cases, no pathological phenotypes distinct from those arising from the absence of MHC-II-mediated Ag presentation have been documented.…”

Section: Discussionmentioning

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%

“…Tg mice and littermate controls were sexmatched, over 8 wk old and housed under conventional conditions. CIITA and H2-Aa knockout mice backcrossed onto a C57B6/J background were provided by C. H. Chang and H. Bluethmann [25,29]. CIITA-p(III+IV) mice were on a mixed Sv129 Â C57BL/6 background [19].…”

Section: Micementioning

confidence: 99%

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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“…Initial studies found that NLR family member CIITA could regulate the MHC class I gene activation through overexpression system in vitro (Martin et al, 1997;Williams et al, 2003). However, the expression of MHC class I genes was not affected in Ciita-defi cient mice (Chang et al, 1996), suggesting that there may be unidentifi ed regulators for MHC class I genes. As mentioned of NLRC5 was impaired in Stat1 -/-T cells after TCR activation which can promote IFN-γ production.…”

Section: Structure Of Nlrc5mentioning

confidence: 99%

“…Over a decade ago, it was reported that the class II transactivator (CIITA also known as NLRA), was essential for conventional MHC class II gene expression and consequently CD4 + T cell development and activation through genetic study of Ciita-deficient mice (Chang et al, 1996). Therefore, CIITA represents a master regulator of MHC class II gene expression (Williams et al, 1998;LeibundGut-Landmann et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Expression regulation and function of NLRC5

Yao

Qian

2013

Protein Cell

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The NOD like receptors (NLRs), a class of intracellular receptors that respond to pathogen attack or cellular stress, have gained increasing attention. NLRC5, the largest member of the NLR protein family, has recently been identified as a critical regulator of immune responses. While NLRC5 is constitutively and widely expressed, it can be dramatically induced by interferons during pathogen infections. Both in vitro and in vivo studies have demonstrated that NLRC5 is a specifi c and master regulator of major mistocompatibility complex (MHC) class I genes as well as related genes involved in MHC class I antigen presentation. The expression of MHC class I genes is regulated by NLRC5 in coordination with the RFX components through an enhanceosome-dependent manner. And the involvement of NLRC5 in MHC class I mediated CD8 + T cell activation, proliferation and cytotoxicity is proved to be critical for host defense against intracellular bacterial infections. Nevertheless, the role of NLRC5 in innate immunity remains to be further explored. Here, we review the research advances on the structure, expression regulation and function of NLRC5.

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“…MHC class II genes are constitutively expressed in B cells and dendritic cells (DC) and can be induced in macrophages by IFN-γ (Steinman et al, 1999;Reith et al, 2005). Both constitutive and inducible MHC class II gene expression requires the class II transactivator (CIITA) (Reith et al, 2005;Steimle et al, 1993;Chang et al, 1996;LeibundGutLandmann et al, 2004). CIITA is not a DNA binding protein.…”

Section: Introductionmentioning

confidence: 99%

Role of PKCδ in IFN-γ-inducible CIITA gene expression☆

Kwon

Yao

Walter

et al. 2007

Molecular Immunology

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The class II transactivator (CIITA) is a key regulatory factor for MHC class II expression. Here, we demonstrate that PKCδ plays an important role in regulating IFN-γ-inducible CIITA gene expression in macrophages. Inhibition of PKCδ by either a PKCδ inhibitor or a dominant negative (DN) mutant form of PKCδ led to down-regulation of CIITA expression. The decrease in CIITA expression by PKCδ inhibition was in part due to the reduced recruitment of serine 727-phosphorylated Stat1 and histone acetyltransferases to the CIITA promoter. As a result, IFN-γ induced histone acetylation at the CIITA promoter is also compromised. However, inhibition of PKCδ did not affect IRF-1 expression or IRF-1 binding to the CIITA promoter. Therefore, we report, for the first time, that PKCδ is an essential signaling molecule to achieve the maximal expression of CIITA in response to IFN-γ in macrophages. In addition, although IRF-1 is a key transcription factor to activate the IFN-γ inducible CIITA promoter, the effect of PKCδ on CIITA expression is mediated primarily by serine phosphorylation of Stat1.

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Mice Lacking the MHC Class II Transactivator (CIITA) Show Tissue-Specific Impairment of MHC Class II Expression

Cited by 334 publications

References 47 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

Expression regulation and function of NLRC5

Role of PKCδ in IFN-γ-inducible CIITA gene expression☆

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