Regulation of Class II MHC Expression in APCs: Roles of Types I, III, and IV Class II Transactivator

Pai, Rish K.; Askew, David; Boom, W. Henry; Harding, Clifford V.

doi:10.4049/jimmunol.169.3.1326

Cited by 94 publications

(112 citation statements)

References 44 publications

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“…The putative regulatory region acts as a STAT-1-dependent and IRF-1-independent enhancer [43]. In contrast to these findings in human cells, pIII does not seem to be inducible by IFN-+ in primary rat astrocytes [48] or in mouse macrophages [40,49]. Moreover, pIII is not sufficient for driving IFN-+ -induced CIITA and MHCII expression in non-BM-derived cells of the pIV knockout mice [40].…”

Section: Ifn-q -Stimulated Cellsmentioning

confidence: 68%

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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Section: Ifn-q -Stimulated Cellsmentioning

confidence: 68%

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

et al. 2004

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“…Previous studies in primary human monocytes are limited to a single observation that type III CIITA is expressed in freshly isolated cells, albeit at low levels (37). Using primary cells, a recent study found that murine bone marrow-derived macrophages (derived in the presence of M-CSF) and thioglycolate-elicited peritoneal macrophages express low levels of type I CIITA, with types I and IV CIITA induced in IFN-␥-activated cells (38). In addition, macrophages from CIITA PIV knockout mice express CIITA driven from PI following IFN-␥ treatment (34).…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

Hornell

Beresford

Bushey

et al. 2003

The Journal of Immunology

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GM-CSF stimulates the growth and differentiation of hematopoietic progenitors and also affects mature cell function. These effects have led to the use of GM-CSF as a vaccine adjuvant with promising results; however, the mechanisms underlying GM-CSF-mediated immune potentiation are incompletely understood. In this study, we investigated the hypothesis that the immune stimulatory role of GM-CSF is in part due to effects on class II MHC Ag presentation. We find that, in primary human monocytes treated for 24–48 h, GM-CSF increases surface class II MHC expression and decreases the relative level of the invariant chain-derived peptide, CLIP, bound to surface class II molecules. GM-CSF also increases expression of the costimulatory molecules CD86 and CD40, but not the differentiation marker CD1a or CD16. Furthermore, GM-CSF-treated monocytes are better stimulators in a mixed leukocyte reaction. Additional analyses of the class II pathway revealed that GM-CSF increases total protein and RNA levels of HLA-DR, DM, and DOα. Expression of class II transactivator (CIITA) types I and III, but not IV, transcripts increases in response to GM-CSF. Furthermore, GM-CSF increases the amount of CIITA associated with the DR promoter. Thus, our data argue that the proinflammatory role of GM-CSF is mediated in part through increased expression of key molecules involved in the class II MHC pathway via induction of CIITA.

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“…DC have been reported to express all three isoforms of CIITA: type I (expressed only in cells of the monocyte lineage and containing a unique N-terminal caspase recruitment domain), type III (also expressed in B cells), and type IV (whose expression is induced by IFN-␥) (13,(15)(16)(17). Type I and type III CIITA comprise most of the CIITA expressed by immature DC, but maturation induces a precipitous decline in levels of type I and type III CIITA mRNA and protein (16,18). This decrease correlates with the shutdown of MHC class II transcription and the shift from Ag processing to Ag presentation (16).…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Enhanced Production of IL-10 by Dendritic Cells Deficient in CIITA

Yee

Yao

et al. 2005

The Journal of Immunology

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Dendritic cells (DC) are professional APCs that play a critical role in regulating immunity. In DC, maturation-induced changes in MHC class II expression and Ag presentation require transcriptional regulation by CIITA. To study the role of CIITA in DC, we evaluated key cell functions in DC from CIITA-deficient (CIITA−/−) mice. The ability to take up Ag, measured by fluid phase endocytosis, was comparable between CIITA−/− and control DC. Although CIITA−/− DC lack MHC class II, they maintained normal expression of costimulatory molecules CD80, CD86, and CD40. In contrast, CIITA−/− DC activated with LPS or CpG expressed increased IL-10 levels, but normal levels of TNF-α and IL-12 relative to control. Enhanced IL-10 was due to greater IL-10 mRNA in CIITA−/− DC. Aβ−/− DC, which lack MHC class II but express CIITA normally, had exhibited no difference in IL-10 compared with control. When CIITA was cotransfected with an IL-10 promoter-reporter into a mouse monocyte cell line, RAW 264.7, IL-10 promoter activity was decreased. In addition, reintroducing CIITA into CIITA−/− DC reduced production of IL-10. In all, these data suggest that CIITA negatively regulates expression of IL-10, and that CIITA may direct DC function in ways that extend beyond control of MHC class II.

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Regulation of Class II MHC Expression in APCs: Roles of Types I, III, and IV Class II Transactivator

Cited by 94 publications

References 44 publications

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

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

Regulation of the Class II MHC Pathway in Primary Human Monocytes by Granulocyte-Macrophage Colony-Stimulating Factor

Enhanced Production of IL-10 by Dendritic Cells Deficient in CIITA

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