{"doi":"10.1016/j.ajpath.2016.09.009","title":"Toll-Like Receptor 2, Toll-Like Receptor 4, Myeloid Differentiation Response Gene 88, and Toll–IL-1 Receptor Domain-Containing Adaptor-Inducing Interferon-γ (TRIF) Selectively Regulate Susceptibility of P0106-125-Induced Murine Experimental Autoimmune Neuritis","abstract":null,"journal":"The American Journal of Pathology","year":2017,"id":637217,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1654390,"name":"Mirna Mihelcic","orcid":null,"position":1,"is_corresponding":false},{"id":1654391,"name":"Mariana Carstov","orcid":null,"position":2,"is_corresponding":false},{"id":1654392,"name":"Lisa Feind","orcid":null,"position":3,"is_corresponding":false},{"id":1654393,"name":"Eva C. Wieser","orcid":null,"position":4,"is_corresponding":false},{"id":805378,"name":"Julia Schmidt","orcid":"0000-0002-4617-3463","position":5,"is_corresponding":false},{"id":937633,"name":"Olaf Utermöhlen","orcid":null,"position":6,"is_corresponding":false},{"id":470974,"name":"Martina Deckert","orcid":"0000-0002-2468-0608","position":7,"is_corresponding":false},{"id":470978,"name":"Anna Brunn","orcid":"0000-0001-6233-8339","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Toll-Like Receptor 2, Toll-Like Receptor 4, Myeloid Differentiation Response Gene 88, and Toll–IL-1 Receptor Domain-Containing Adaptor-Inducing Interferon-γ (TRIF) Selectively Regulate Susceptibility of P0106-125-Induced Murine Experimental Autoimmune Neuritis","abstract":"The functional relevance of the innate immune system has not yet been dissected in P0<sub>106-125</sub>-induced murine experimental autoimmune neuritis. Therefore, the role of Toll-like receptor (TLR) 2, TLR4, myeloid differentiation response gene 88, and Toll-IL-1 receptor domain-containing adaptor-inducing interferon-γ (TRIF), factors critically involved in the TLR signaling pathway, was studied in experimental autoimmune neuritis. In the absence of TLR2, TLR4, myeloid differentiation response gene 88, or TRIF, the clinical course was significantly attenuated compared to wild-type mice. This could be attributed to impaired NF-κB activation, as shown by the absence of nuclear translocation of RelA with a decreased expression of IL-6, IL-12p40, and IL-17A. Remarkably, P0<sub>106-125</sub>-immunized TLR2<sup>0/0</sup> mice exhibited a delayed recovery as compared to TLR4<sup>0/0</sup> mice, which was because of an impaired T helper cell 2 polarization. Immunized TLR2<sup>0/0</sup> mice were unable to induce OX40 and OX40L by matrix metalloproteinase-2 on splenic dendritic cells. Subsequently, M2 polarization was impaired and macrophages were unable to sufficiently induce T regulatory cells (T<sub>regs</sub>). Thus, in the recovery phase, T<sub>regs</sub> were significantly increased in TLR4<sup>0/0</sup> mice as compared to wild-type mice, whereas T<sub>regs</sub> in immunized TLR2<sup>0/0</sup> mice were only slightly increased. Our data highlight the relevance of innate immunity and, especially, the tight interaction between the innate and the adaptive immune system, which should be considered for therapeutic approaches of autoimmune diseases.","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27842213","pmcid":null,"openalex_id":"https://openalex.org/W2561504160","authors":[],"funders":[{"funder_name":"Else Kröner-Fresenius-Stiftung","grant_id":"2010_A 139","title":null}],"total_grants":1,"fwci":0.4229,"citation_percentile":0.64761647,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":2},{"year":2020,"count":1},{"year":2025,"count":1}],"oa_status":"closed","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0002944016304126?httpAccept=text/plain","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0002944016304126?httpAccept=text/xml","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ajpath.2016.09.009","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27842213","host_type":"repository"}],"fields_of_study":["Immune Response and Inflammation","Cytokine Signaling Pathways and Interactions","interferon and immune responses","Adaptor Proteins, Vesicular Transport","Animals","Axons","CD4-Positive T-Lymphocytes","Complement C1q","Disease Progression","Disease Susceptibility","Immunoglobulin G","Immunoglobulin M","Interferon-gamma","Lymphocyte Count","Macrophage Activation","Matrix Metalloproteinase 2","Mice, Inbred C57BL","Muscle, Skeletal","Myelin P0 Protein","Myeloid Differentiation Factor 88","NF-kappa B","Neuritis, Autoimmune, Experimental","OX40 Ligand","RNA, Messenger","Receptors, OX40","Sciatic Nerve","Signal Transduction","Spleen","Toll-Like Receptor 2","Toll-Like Receptor 4"],"mesh_terms":["Animals","Axons","Disease Susceptibility","Immunoglobulin G","Immunoglobulin M","Interferon-gamma","Macrophage Activation","Mice, Inbred C57BL","Neuritis, Autoimmune, Experimental","RNA, Messenger","Sciatic Nerve","Spleen","Signal Transduction","CD4-Positive T-Lymphocytes","Complement C1q","NF-kappa B","Disease Progression","Muscle, Skeletal","Lymphocyte Count","Myelin P0 Protein","Matrix Metalloproteinase 2","Adaptor Proteins, Vesicular Transport","Toll-Like Receptor 2","Toll-Like Receptor 4","Receptors, OX40","OX40 Ligand","Myeloid Differentiation Factor 88"],"keywords":["TRIF","Toll-like receptor","Toll","Receptor","Signal transducing adaptor protein","Interleukin-21 receptor","Cell biology","Biology","Chemistry","Immunology","Innate immune system","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T18:33:52.589164Z","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":[]}