| First Author | Buxadé M | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 11 | Pages | 2901-2918 |
| PubMed ID | 30327417 | Mgi Jnum | J:269768 |
| Mgi Id | MGI:6272997 | Doi | 10.1084/jem.20180314 |
| Citation | Buxade M, et al. (2018) Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5. J Exp Med 215(11):2901-2918 |
| abstractText | MHCII in antigen-presenting cells (APCs) is a key regulator of adaptive immune responses. Expression of MHCII genes is controlled by the transcription coactivator CIITA, itself regulated through cell type-specific promoters. Here we show that the transcription factor NFAT5 is needed for expression of Ciita and MHCII in macrophages, but not in dendritic cells and other APCs. NFAT5-deficient macrophages showed defective activation of MHCII-dependent responses in CD4(+) T lymphocytes and attenuated capacity to elicit graft rejection in vivo. Ultrasequencing analysis of NFAT5-immunoprecipitated chromatin uncovered an NFAT5-regulated region distally upstream of Ciita This region was required for CIITA and hence MHCII expression, exhibited NFAT5-dependent characteristics of active enhancers such as H3K27 acetylation marks, and required NFAT5 to interact with Ciita myeloid promoter I. Our results uncover an NFAT5-regulated mechanism that maintains CIITA and MHCII expression in macrophages and thus modulates their T lymphocyte priming capacity. |
