Ciita, also known as the MHC class II transactivator, is a master regulator of MHC class II (MHC-II) gene transcription. As an NLR (nucleotide-binding domain, leucine-rich-repeat containing) protein, it plays a critical role in the activation and regulation of adaptive immunity by enabling antigen presentation to CD4+ T cells [1,2,3,8]. The regulation of MHC-II expression is largely controlled by the differential expression of Ciita [3].

In terms of its function in diseases, FBXO11, an E3 ligase, regulates Ciita protein level through ubiquitination-mediated degradation, and its expression is negatively correlated with MHC-II in normal and cancer tissues, suggesting FBXO11 as a potential biomarker for cancer [1]. Ciita also has a dual role in intrinsic and adaptive immunity, acting as a restriction factor for human retroviruses and a tool to induce MHC-II expression in cancer cells [2,5]. In a myeloma model, osteocyte-expressed Ciita contributes to myeloma-induced bone lesions by upregulating osteolytic cytokines [4]. In a Parkinson's disease rat model, Ciita regulates susceptibility to PD-like pathology through changes in immune cells and TNF levels [6]. Additionally, variants of Ciita may contribute to the development of endometriosis, as a novel missense variant in Ciita affected cell migration and invasion ability [7]. In bladder cancer, IFNγ -driven, tumor cell intrinsic expression of Ciita is required for BCG-induced tumor immunity, independent of MHC-II [9]. CIITA -transduced glioblastoma cells can uncover a rich repertoire of clinically relevant tumor-associated HLA-II antigens, suggesting potential therapeutic applications [10].

In summary, Ciita is crucial for regulating MHC-II gene expression and immune responses. Its study using various models has revealed its diverse roles in multiple diseases, including cancer, myeloma, Parkinson's disease, and endometriosis. These findings provide insights into disease mechanisms and potential therapeutic strategies.