{"doi":"10.17615/1h3p-5475","title":"The Innate Immune Sensor NLRC3 Acts as a Rheostat that Fine-Tunes T Cell Responses in Infection and Autoimmunity","abstract":"NLRC3 limits inflammatory signaling in myeloid cells, but its role in T cells has been unclear. Uchimura et al. reveal that T cell expression of Nlrc3 restricts autoimmune and virus-specific CD4 + T cell responses by attenuating T cell signaling and metabolic pathways in CD4 + T cells. © 2018 Elsevier Inc.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-γ 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-κB 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.","journal":"UNC Libraries","year":2021,"id":212627,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9447,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":803587,"name":"Y. Oyama","orcid":null,"position":1,"is_corresponding":false},{"id":787633,"name":"W.J. Brickey","orcid":null,"position":2,"is_corresponding":false},{"id":803588,"name":"B. Johnson","orcid":null,"position":3,"is_corresponding":false},{"id":803589,"name":"K.D. Cook","orcid":null,"position":4,"is_corresponding":false},{"id":118839,"name":"L. CHEN","orcid":null,"position":5,"is_corresponding":false},{"id":52179,"name":"H. Guo","orcid":null,"position":6,"is_corresponding":false},{"id":794605,"name":"J.P.Y. Ting","orcid":null,"position":7,"is_corresponding":false},{"id":591494,"name":"I. Misumi","orcid":null,"position":8,"is_corresponding":false},{"id":803590,"name":"E. Rampanelli","orcid":null,"position":9,"is_corresponding":false},{"id":591496,"name":"T. Uchimura","orcid":null,"position":10,"is_corresponding":false},{"id":803544,"name":"J.E. Wilson","orcid":null,"position":11,"is_corresponding":false},{"id":175915,"name":"M. Deng","orcid":null,"position":12,"is_corresponding":false},{"id":591495,"name":"J.K. Whitmire","orcid":null,"position":13,"is_corresponding":false},{"id":803591,"name":"Jenna K Tam","orcid":null,"position":14,"is_corresponding":false},{"id":794602,"name":"W.-C. Chou","orcid":null,"position":15,"is_corresponding":false},{"id":787635,"name":"A. Petrucelli","orcid":null,"position":16,"is_corresponding":false},{"id":416011,"name":"X. Tan","orcid":"0000-0003-3358-8157","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:52:27.434608Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}