| First Author | Hermann-Kleiter N | Year | 2008 |
| Journal | Immunity | Volume | 29 |
| Issue | 2 | Pages | 205-16 |
| PubMed ID | 18701084 | Mgi Jnum | J:139691 |
| Mgi Id | MGI:3809371 | Doi | 10.1016/j.immuni.2008.06.008 |
| Citation | Hermann-Kleiter N, et al. (2008) The Nuclear Orphan Receptor NR2F6 Suppresses Lymphocyte Activation and T Helper 17-Dependent Autoimmunity. Immunity 29(2):205-16 |
| abstractText | The protein kinase C (PKC) family of serine-threonine kinases plays a central role in T lymphocyte activation. Here, we identify NR2F6, a nuclear zinc-finger orphan receptor, as a critical PKC substrate and essential regulator of CD4(+) T cell activation responses. NR2F6 potently antagonized the ability of T helper 0 (Th0) and Th17 CD4(+) T cells to induce expression of key cytokine genes such as interleukin-2 (IL-2) and IL-17. Mechanistically, NR2F6 directly interfered with the DNA binding of nuclear factor of activated T cells (NF-AT):activator protein 1 (AP-1) but not nuclear factor kappaB (NF-kappaB) and, subsequently, transcriptional activity of the NF-AT-dependent IL-17A cytokine promoter. Consistent with our model, Nr2f6-deficient mice had hyperreactive lymphocytes, developed a late-onset immunopathology, and were hypersusceptible to Th17-dependent experimental autoimmune encephalomyelitis. Our study establishes NR2F6 as a transcriptional repressor of IL-17 expression in Th17-differentiated CD4(+) T cells in vitro and in vivo. |
