Otten Luc A, Leibundgut-Landmann Salomé, Huarte Joachim, Kos-Braun Isabelle C, Lavanchy Christine, Barras Emmanuèle, Borisch Bettina, Steimle Viktor, Acha-Orbea Hans, Reith Walter
Department of Pathology and Immunology, University of Geneva Medical School, Switzerland.
Eur J Immunol. 2006 Jun;36(6):1548-58. doi: 10.1002/eji.200535687.
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-gamma, 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.
CIITA是MHC II类分子（MHC-II）及参与抗原呈递的辅助基因表达的主要调控因子。最近有研究表明，CIITA还调控免疫系统内外众多具有不同功能的其他基因。为确定这些基因在体内是否确实是CIITA的相关靶点，我们研究了它们在CIITA转基因小鼠和CIITA缺陷小鼠中的表达。与CIITA对MHC-II及相关基因的决定性调控不同，我们发现9个推定的非MHC靶基因（Eif3s2、Kpna6、Tap1、Yars、Col1a2、Ctse、Ptprr、Tnfsf6和Plxna1）在所有检测的细胞类型中均独立于CIITA。确实发现另外两个分别编码IL-4和IFN-γ的靶基因在CIITA转基因CD4(+) T细胞中分别上调和下调。然而，在单个转基因T细胞水平上，MHC-II表达与这种Th2偏向之间没有相关性，表明是CIITA的间接调控。这些结果表明，MHC-II限制的抗原呈递及其对T细胞的间接影响仍然是CIITA在体内直接控制的唯一途径。它们还意味着精确调控的MHC-II表达对于维持适当的Th1-Th2平衡至关重要。
