| First Author | Uchimura T | Year | 2018 |
| Journal | Immunity | Volume | 49 |
| Issue | 6 | Pages | 1049-1061.e6 |
| PubMed ID | 30566882 | Mgi Jnum | J:295063 |
| Mgi Id | MGI:6459605 | Doi | 10.1016/j.immuni.2018.10.008 |
| Citation | Uchimura T, et al. (2018) The Innate Immune Sensor NLRC3 Acts as a Rheostat that Fine-Tunes T Cell Responses in Infection and Autoimmunity. Immunity 49(6):1049-1061.e6 |
| abstractText | Appropriate immune responses require a fine balance between immune activation and attenuation. NLRC3, a non-inflammasome-forming member of the NLR innate immune receptor family, attenuates inflammation in myeloid cells and proliferation in epithelial cells. T lymphocytes express the highest amounts of Nlrc3 transcript where its physiologic relevance is unknown. We show that NLRC3 attenuated interferon-gamma and TNF expression by CD4(+) T cells and reduced T helper 1 (Th1) and Th17 cell proliferation. Nlrc3(-/-) mice exhibited increased and prolonged CD4(+) T cell responses to lymphocytic choriomeningitis virus infection and worsened experimental autoimmune encephalomyelitis (EAE). These functions of NLRC3 were executed in a T-cell-intrinsic fashion: NLRC3 reduced K63-linked ubiquitination of TNF-receptor-associated factor 6 (TRAF6) to limit NF-kappaB activation, lowered phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and diminished glycolysis and oxidative phosphorylation. This study reveals an unappreciated role for NLRC3 in attenuating CD4(+) T cell signaling and metabolism. |
