| http://purl.uniprot.org/citations/31015190 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31015190 | http://www.w3.org/2000/01/rdf-schema#comment | "Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal disorder characterized by the overactivation of T cells and macrophages that excessively produce proinflammatory cytokines, including interferon-γ (IFN-γ). Previously, we reported that the JAK inhibitor ruxolitinib dampens T-cell activation and lessens inflammation in a model of HLH in which perforin-deficient (Prf1 -/-) mice are infected with lymphocytic choriomeningitis virus (LCMV). Ruxolitinib inhibits signaling downstream of IFN-γ, as well as several other JAK-dependent cytokines. As a consequence, it remained unclear whether ruxolitinib was exerting its beneficial effects in HLH by inhibiting IFN-γ signaling or by targeting signaling initiated by other proinflammatory cytokines. To address this question, we compared the effects of ruxolitinib with those obtained using an IFN-γ-neutralizing antibody (αIFN-γ) in 2 murine HLH models. In both models, ruxolitinib and αIFN-γ reduced inflammation-associated anemia, indicating that ruxolitinib operates in an IFN-γ-dependent manner to reverse this HLH manifestation. In contrast, the number and activation status of T cells and neutrophils, as well as their infiltration into tissues, were significantly reduced following treatment with ruxolitinib, but they remained unchanged or were increased following treatment with αIFN-γ. Notably, despite discontinuation of ruxolitinib, LCMV-infected Prf1 -/- mice exhibited enhanced survival compared with mice in which αIFN-γ was discontinued. This protective effect could be mimicked by transient treatment with αIFN-γ and a neutrophil-depleting antibody. Thus, ruxolitinib operates through IFN-γ-dependent and -independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and neutrophils, with the latter representing an unappreciated and understudied cell type that contributes to HLH pathogenesis."xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood.2019000761"xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/author | "Verbist K.C."xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/author | "Nichols K.E."xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/author | "Tillman H."xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/author | "Bassett R."xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/author | "Albeituni S."xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/author | "Picarsic J."xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/author | "Tedrick P.E."xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/pages | "147-159"xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/title | "Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis."xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://purl.uniprot.org/core/volume | "134"xsd:string |
| http://purl.uniprot.org/citations/31015190 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31015190 |
| http://purl.uniprot.org/citations/31015190 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/31015190 |
| http://purl.uniprot.org/uniprot/#_A2RSY7-mappedCitation-31015190 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31015190 |
| http://purl.uniprot.org/uniprot/#_P10820-mappedCitation-31015190 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31015190 |
| http://purl.uniprot.org/uniprot/A2RSY7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31015190 |
| http://purl.uniprot.org/uniprot/P10820 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/31015190 |