{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:16:27Z","timestamp":1787008587898,"version":"build-2736575974"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by an aberrant immune response against host tissues. It can arise from diverse triggers like infection, inflammation, malignancy, genetic defects, or therapy-related factors. Cytokine storm, capillary leak syndrome, cytokine release syndrome, and macrophage activation syndrome are the different faces of this chimera, and each of them displays significant clinical variability associated with high mortality. The pathogenesis of both primary and secondary HLH generally follows a similar pattern, involving excessive activation of macrophages and uncontrolled destruction of reticuloendothelial tissues. Environmental triggers cause exaggerated activation of innate immune cells in genetically predisposed individuals. This process is further driven by the release of multiple cytokines and soluble mediators that sustain ongoing inflammation and cause subsequent target organ damage. Biomarkers, including cytokines and inflammatory mediators, are crucial for early detection and monitoring treatment response. Persistent immune activation and inadequate resolution mechanisms result in a destructive inflammatory cascade or \u201cimmunological massacre\u201d. Animal models of HLH and MAS elucidate the roles of impaired cytotoxicity, IFN-\u03b3, TLR signaling, and inflammatory cytokines in disease pathogenesis. Trigger-specific differences highlight the involvement of CD8+ T cells, NK cells, macrophages, and cytokines. Therapeutic strategies include cytokine neutralization, adoptive T-cell transfer, and mTOR inhibition. Timely diagnosis and prompt initiation of therapy are essential to mitigate the serious consequences of HLH and improve long-term outcomes.<\/jats:p>","DOI":"10.1093\/cei\/uxaf036","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T07:14:58Z","timestamp":1748070898000},"source":"Crossref","is-referenced-by-count":6,"title":["The pathophysiology of hemophagocytic lympho-histiocytosis (HLH) syndrome and insights from animal models"],"prefix":"10.1093","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1694-7795","authenticated-orcid":false,"given":"Sayan","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, King George Medical University , Lucknow ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puneet","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Rheumatology, King George Medical University , Lucknow ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"2025062505515982000_CIT0001","doi-asserted-by":"publisher","first-page":"e27929","DOI":"10.1002\/pbc.27929","article-title":"Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO)","volume":"66","author":"Jordan","year":"2019","journal-title":"Pediatric Blood & Cancer"},{"key":"2025062505515982000_CIT0002","doi-asserted-by":"publisher","first-page":"507","DOI":"10.5858\/arpa.2020-0802-RA","article-title":"Hemophagocytic lymphohistiocytosis","volume":"146","author":"Ponnatt","year":"2022","journal-title":"Arch Pathol Laborat Med"},{"key":"2025062505515982000_CIT0003","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1002\/JLB.MR0718-269R","article-title":"Mechanisms of natural killer cell-mediated cellular cytotoxicity","volume":"105","author":"Prager","year":"2019","journal-title":"J Leukoc Biol"},{"key":"2025062505515982000_CIT0004","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1055\/s-0029-1237386","article-title":"Hemophagocytic lymphohistiocytosis: When the immune system runs amok","volume":"221","author":"Janka","year":"2009","journal-title":"Klin Padiatr"},{"key":"2025062505515982000_CIT0005","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1309\/AJCP4ZDKJ4ICOUAT","article-title":"Hemophagocytic lymphohistiocytosis: an update on diagnosis and pathogenesis","volume":"139","author":"Rosado","year":"2013","journal-title":"Am J Clin Pathol"},{"key":"2025062505515982000_CIT0006","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1146\/annurev-pathol-020117-043625","article-title":"Hemophagocytic lymphohistiocytosis","volume":"13","author":"Al-Samkari","year":"2018","journal-title":"Annu Rev Pathol"},{"key":"2025062505515982000_CIT0007","doi-asserted-by":"publisher","first-page":"4041","DOI":"10.1182\/blood-2011-03-278127","article-title":"How I treat hemophagocytic lymphohistiocytosis","volume":"118","author":"Jordan","year":"2011","journal-title":"Blood"},{"key":"2025062505515982000_CIT0008","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fped.2016.00047","article-title":"Hemophagocytic lymphohistiocytosis in children: pathogenesis and treatment","volume":"4","author":"Ishii","year":"2016","journal-title":"Front Pediatr"},{"key":"2025062505515982000_CIT0009","doi-asserted-by":"publisher","first-page":"e26264","DOI":"10.1002\/pbc.26264","article-title":"Clinical presentation and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in China: a retrospective multicenter study","volume":"64","author":"Xu","year":"2017","journal-title":"Pediatric Blood Cancer"},{"key":"2025062505515982000_CIT0010","doi-asserted-by":"publisher","first-page":"5824","DOI":"10.1182\/blood-2010-04-282392","article-title":"Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation","volume":"116","author":"Marsh","year":"2010","journal-title":"Blood"},{"key":"2025062505515982000_CIT0011","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/imr.12791","article-title":"Signaling pathways involved in the T-cell-mediated immunity against Epstein-Barr virus: lessons from genetic diseases","volume":"291","author":"Latour","year":"2019","journal-title":"Immunol Rev"},{"key":"2025062505515982000_CIT0012","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s12985-023-02187-9","article-title":"Epstein-Barr virus infection: the micro and macro worlds","volume":"20","author":"Huang","year":"2023","journal-title":"Virol J"},{"key":"2025062505515982000_CIT0013","doi-asserted-by":"publisher","first-page":"e3110","DOI":"10.1093\/cid\/ciaa1463","article-title":"Assessment of the hemophagocytic lymphohistiocytosis HScore in patients with coronavirus disease 2019","volume":"73","author":"Clark","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2025062505515982000_CIT0014","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1186\/s13256-023-03967-1","article-title":"Hemophagocytic lymphohistiocytosis as a rare complication of dengue haemorrhagic fever: a case report","volume":"17","author":"Pradeep","year":"2023","journal-title":"J Med Case Rep"},{"key":"2025062505515982000_CIT0015","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.idcr.2017.03.013","article-title":"Severe dengue due to secondary hemophagocytic lymphohistiocytosis: a case study","volume":"8","author":"Ray","year":"2017","journal-title":"IDCases"},{"key":"2025062505515982000_CIT0016","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1093\/cid\/ciz499","article-title":"Dengue infection complicated by hemophagocytic lymphohistiocytosis: experiences from 180 patients with severe dengue","volume":"70","author":"Kan","year":"2020","journal-title":"Clin infect Diseases"},{"key":"2025062505515982000_CIT0017","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1182\/asheducation-2015.1.177","article-title":"Pathophysiology and epidemiology of hemophagocytic lymphohistiocytosis","volume":"2015","author":"Allen","year":"2015","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"2025062505515982000_CIT0018","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.hoc.2015.06.009","article-title":"Hemophagocytic lymphohistiocytosis in adults","volume":"29","author":"Campo","year":"2015","journal-title":"Hematol Oncol Clin North Am"},{"key":"2025062505515982000_CIT0019","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1016\/S0140-6736(13)61048-X","article-title":"Adult haemophagocytic syndrome","volume":"383","author":"Ramos-Casals","year":"2014","journal-title":"Lancet (London, England)"},{"key":"2025062505515982000_CIT0020","first-page":"13","article-title":"Epstein-Barr virus-positive lymphoma-associated hemophagocytic syndrome: a retrospective, single-center study of 51 patients","volume":"11","author":"Zhao","year":"2022","journal-title":"Frontiers in immunology"},{"key":"2025062505515982000_CIT0021","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s00277-011-1239-7","article-title":"Possible prediction of underlying lymphoma by high sIL-2R\/ferritin ratio in hemophagocytic syndrome","volume":"91","author":"Tabata","year":"2012","journal-title":"Ann Hematol"},{"key":"2025062505515982000_CIT0022","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1067\/mpd.2003.110","article-title":"Natural killer cell dysfunction in patients with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome","volume":"142","author":"Grom","year":"2003","journal-title":"J Pediatr"},{"key":"2025062505515982000_CIT0023","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.3390\/microorganisms10091848","article-title":"Advanced glycation end products in health and disease","volume":"10","author":"Reddy","year":"2022","journal-title":"Microorganisms."},{"key":"2025062505515982000_CIT0024","doi-asserted-by":"publisher","first-page":"S73","DOI":"10.2337\/diab.45.3.s73","article-title":"Advanced glycation end products and their recognition by macrophage and macrophage-derived cells","volume":"45","author":"Horiuchi","year":"1996","journal-title":"Diabetes"},{"key":"2025062505515982000_CIT0025","first-page":"8","article-title":"S100 Proteins as an important regulator of macrophage inflammation","volume":"5","author":"Xia","year":"2018","journal-title":"Frontiers in immunology"},{"key":"2025062505515982000_CIT0026","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.3390\/cells11152274","article-title":"Multifunctional role of S100 protein family in the immune system: an update","volume":"11","author":"Singh","year":"2022","journal-title":"Cells."},{"key":"2025062505515982000_CIT0027","first-page":"13","article-title":"The role of HMGB1 in rheumatic diseases","volume":"17","author":"Dong","year":"2022","journal-title":"Frontiers in immunology"},{"key":"2025062505515982000_CIT0028","doi-asserted-by":"publisher","first-page":"166184","DOI":"10.1016\/j.bbadis.2021.166184","article-title":"Extracellular HMGB1 augments macrophage inflammation by facilitating the endosomal accumulation of ALD-DNA via TLR2\/4-mediated endocytosis","volume":"1867","author":"Lu","year":"2021","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"2025062505515982000_CIT0029","doi-asserted-by":"crossref","first-page":"P57","DOI":"10.1186\/1546-0096-12-S1-P57","article-title":"Cytokine active disulfide-HMGB1 increased during severe macrophage activation syndrome","volume":"12","author":"Schierbeck","year":"2014","journal-title":"Pediatr Rheumatol"},{"key":"2025062505515982000_CIT0030","doi-asserted-by":"publisher","first-page":"5921","DOI":"10.3390\/ijms25115921","article-title":"Pathogenesis of hemophagocytic lymphohistiocytosis\/macrophage activation syndrome: a case report and review of the literature","volume":"25","author":"Gioia","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2025062505515982000_CIT0031","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1203\/00006450-199810000-00001","article-title":"Defective natural killer cell function in patients with hemophagocytic lymphohistiocytosis and in first degree relatives","volume":"44","author":"Sullivan","year":"1998","journal-title":"Pediatr Res"},{"key":"2025062505515982000_CIT0032","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1182\/blood.2020006097","article-title":"NK cells: energized yet exhausted in adult HLH","volume":"136","author":"Nichols","year":"2020","journal-title":"Blood"},{"key":"2025062505515982000_CIT0033","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/s12276-024-01182-6","article-title":"Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis\/macrophage activation syndrome: a translational perspective","volume":"56","author":"Nguyen","year":"2024","journal-title":"Exp Mol Med"},{"key":"2025062505515982000_CIT0034","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3389\/fimmu.2019.00119","article-title":"The immunology of macrophage activation syndrome","volume":"10","author":"Crayne","year":"2019  1","journal-title":"Front Immunol [Internet]"},{"key":"2025062505515982000_CIT0035","first-page":"14","article-title":"Insights into the cellular pathophysiology of familial hemophagocytic lymphohistiocytosis","volume":"14","author":"Steen","year":"2023","journal-title":"Front Immunol [Internet]"},{"key":"2025062505515982000_CIT0036","doi-asserted-by":"publisher","first-page":"e2413162121","DOI":"10.1073\/pnas.2413162121","article-title":"Enforced CARD11\/MALT1 signaling in dendritic cells triggers hemophagocytic lymphohistiocytosis","volume":"121","author":"Isay","year":"2024","journal-title":"Proc Natl Acad Sci USA"},{"key":"2025062505515982000_CIT0037","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1182\/blood.2020010236","article-title":"HLH or sepsis: the truth is in the T cells","volume":"137","author":"Hines","year":"2021","journal-title":"Blood"},{"key":"2025062505515982000_CIT0038","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.jaci.2015.12.1314","article-title":"IL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis","volume":"138","author":"Humblet-Baron","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"2025062505515982000_CIT0039","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1111\/imr.13298","article-title":"Hemophagocytic lymphohistiocytosis: a disorder of T cell activation, immune regulation, and distinctive immunopathology","volume":"322","author":"Jordan","year":"2024","journal-title":"Immunol Rev"},{"key":"2025062505515982000_CIT0040","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.3760\/cma.j.cn112137-20220101-00003","article-title":"[Precise diagnosis and treatment of hemophagocytic lymphohistiocytosis guided by cytokine patterns]","volume":"102","author":"Xu","year":"2022","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"2025062505515982000_CIT0041","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/cei.13543","article-title":"The role of interleukin-18 in the diagnosis and monitoring of hemophagocytic lymphohistiocytosis\/macrophage activation syndrome \u2013 a systematic review","volume":"203","author":"Krei","year":"2021","journal-title":"Clin Exp Immunol"},{"key":"2025062505515982000_CIT0042","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1164\/rccm.201912-2322ED","article-title":"Using the extremes of human inflammation to understand the transcriptional control of IL-18","volume":"201","author":"LaRivi\u00e8re","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"2025062505515982000_CIT0043","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1136\/annrheumdis-2017-212608","article-title":"Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still\u2019s disease","volume":"77","author":"Gabay","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"2025062505515982000_CIT0044","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1016\/j.jaci.2016.10.022","article-title":"Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition","volume":"139","author":"Canna","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"2025062505515982000_CIT0045","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1365-2141.1994.tb04905.x","article-title":"Involvement of interferon-\u03b3 and macrophage colony-stimulating factor in pathogenesis of haemophagocytic lymphohistiocytosis in adults","volume":"87","author":"Akashi","year":"1994","journal-title":"Br J Haematol"},{"key":"2025062505515982000_CIT0046","doi-asserted-by":"publisher","first-page":"887","DOI":"10.21037\/atm-20-3127","article-title":"Successful treatment of secondary macrophage activation syndrome with emapalumab in a patient with newly diagnosed adult-onset Still\u2019s disease: case report and review of the literature","volume":"8","author":"Gabr","year":"2020","journal-title":"Ann Transl Med."},{"key":"2025062505515982000_CIT0047","first-page":"11","article-title":"Case report: emapalumab for active disease control prior to hematopoietic stem cell transplantation in refractory systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome","volume":"11","author":"Chellapandian","year":"2023","journal-title":"Front Pediatr [Internet]"},{"key":"2025062505515982000_CIT0048","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1016\/j.jaci.2022.06.017","article-title":"Excessive IL-10 and IL-18 trigger hemophagocytic lymphohistiocytosis\u2013like hyperinflammation and enhanced myelopoiesis","volume":"150","author":"Tang","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"2025062505515982000_CIT0049","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1186\/s13023-021-01973-4","article-title":"Increased levels of serum interleukin-10 are associated with poor outcome in adult hemophagocytic lymphohistiocytosis patients","volume":"16","author":"Zhou","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"2025062505515982000_CIT0050","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s12933-022-01535-3","article-title":"Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study","volume":"21","author":"Sabbatinelli","year":"2022","journal-title":"Cardiovasc Diabetol"},{"key":"2025062505515982000_CIT0051","first-page":"13","article-title":"Soluble receptor for advanced glycation end product is involved in the inflammatory response of human adenovirus-infected patients","volume":"7","author":"Xu","year":"2022","journal-title":"Frontiers in Microbiology"},{"key":"2025062505515982000_CIT0052","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1365-2567.2008.02813.x","article-title":"Mechanisms of regulatory T-cell suppression \u2013 a diverse arsenal for a moving target","volume":"124","author":"Sojka","year":"2008","journal-title":"Immunology"},{"key":"2025062505515982000_CIT0053","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1007\/s10875-020-00950-z","article-title":"Biomarkers for early diagnosis of hemophagocytic lymphohistiocytosis in critically ill patients","volume":"41","author":"Debaugnies","year":"2021","journal-title":"J Clin Immunol"},{"key":"2025062505515982000_CIT0054","doi-asserted-by":"publisher","first-page":"5359","DOI":"10.1182\/blood-2023-178867","article-title":"Inflammatory markers in hemophagocytic lymphohistiocytosis\u2014a single centre study","volume":"142","author":"Spaner","year":"2023","journal-title":"Blood"},{"key":"2025062505515982000_CIT0055","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13052-016-0262-7","article-title":"Comparison of Th1\/Th2 cytokine profiles between primary and secondary haemophagocytic lymphohistiocytosis","volume":"42","author":"Chen","year":"2016","journal-title":"Italian J Pediatr"},{"key":"2025062505515982000_CIT0056","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1146\/annurev-med-061813-012806","article-title":"Pathogenesis of macrophage activation syndrome and potential for cytokine-directed therapies","volume":"66","author":"Schulert","year":"2015","journal-title":"Annu Rev Med"},{"key":"2025062505515982000_CIT0057","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s13023-020-01390-z","article-title":"Genotype characteristics and immunological indicator evaluation of 311 hemophagocytic lymphohistiocytosis cases in China","volume":"15","author":"Zhang","year":"2020","journal-title":"Orphanet J Rare Dis"},{"key":"2025062505515982000_CIT0058","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s00277-023-05132-6","article-title":"Serum cytokine pattern in children with hemophagocytic lymphohistiocytosis","volume":"102","author":"Ou","year":"2023","journal-title":"Ann Hematol"},{"key":"2025062505515982000_CIT0059","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1182\/blood-2003-10-3413","article-title":"An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder","volume":"104","author":"Jordan","year":"2004","journal-title":"Blood"},{"key":"2025062505515982000_CIT0060","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/emmm.200900009","article-title":"Neutralization of IFN\u03b3 defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice","volume":"1","author":"Schmid","year":"2009","journal-title":"EMBO Mol Med"},{"key":"2025062505515982000_CIT0061","doi-asserted-by":"publisher","first-page":"6582","DOI":"10.1182\/blood-2011-01-329607","article-title":"Disruption of MyD88 signaling suppresses hemophagocytic lymphohistiocytosis in mice","volume":"117","author":"Krebs","year":"2011","journal-title":"Blood"},{"key":"2025062505515982000_CIT0062","first-page":"161","article-title":"Interferon-\u03b3\u2013mediated immunopathology potentiated by toll-like receptor 9 activation in a murine model of macrophage activation syndrome. Arthritis &","volume":"71","author":"Weaver","year":"2019","journal-title":"Rheumatology"},{"key":"2025062505515982000_CIT0063","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.4049\/jimmunol.2000168","article-title":"Production of IL-18 binding protein by radiosensitive and radioresistant cells in cpg-induced macrophage activation syndrome","volume":"205","author":"Harel","year":"2020","journal-title":"J Immunol (Baltimore, Md. : 1950)"},{"key":"2025062505515982000_CIT0064","doi-asserted-by":"publisher","first-page":"2264","DOI":"10.1172\/JCI43157","article-title":"Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice","volume":"121","author":"Behrens","year":"2011","journal-title":"J Clin Invest"},{"key":"2025062505515982000_CIT0065","doi-asserted-by":"publisher","first-page":"e147593","DOI":"10.1172\/jci.insight.147593","article-title":"IFN-\u03b3 is essential for alveolar macrophage-driven pulmonary inflammation in macrophage activation syndrome","volume":"6","author":"Gao","year":"2021","journal-title":"JCI Insight"},{"key":"2025062505515982000_CIT0066","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1002\/art.38359","article-title":"Systemic juvenile idiopathic arthritis\u2013like syndrome in mice following stimulation of the immune system with freund\u2019s complete adjuvant: regulation by interferon-\u03b3","volume":"66","author":"Avau","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"2025062505515982000_CIT0067","doi-asserted-by":"publisher","first-page":"2654","DOI":"10.4049\/jimmunol.1800468","article-title":"Insufficient IL-10 production as a mechanism underlying the pathogenesis of systemic juvenile idiopathic arthritis","volume":"201","author":"Imbrechts","year":"2018","journal-title":"J Immunol (Baltimore, Md. : 1950)"},{"key":"2025062505515982000_CIT0068","doi-asserted-by":"publisher","first-page":"3339","DOI":"10.4049\/jimmunol.1900510","article-title":"Regulatory role for NK cells in a mouse model of systemic juvenile idiopathic arthritis","volume":"203","author":"Vandenhaute","year":"2019","journal-title":"J Immunol (Baltimore, Md. : 1950)"},{"key":"2025062505515982000_CIT0069","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1002\/art.42104","article-title":"Role for granulocyte colony-stimulating factor in neutrophilic extramedullary myelopoiesis in a murine model of systemic juvenile idiopathic arthritis","volume":"74","author":"Malengier-Devlies","year":"2022","journal-title":"Arthritis Rheumatology"},{"key":"2025062505515982000_CIT0070","first-page":"12","article-title":"Lung functioning and inflammation in a mouse model of systemic juvenile idiopathic arthritis","volume":"12","author":"Malengier-Devlies","year":"2021","journal-title":"Front Immunol [Internet]"},{"key":"2025062505515982000_CIT0071","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/art.40498","article-title":"IL1RN Variation influences both disease susceptibility and response to recombinant human interleukin-1 receptor antagonist therapy in systemic juvenile idiopathic arthritis","volume":"70","author":"Arthur","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"2025062505515982000_CIT0072","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13075-023-03032-8","article-title":"Mouse models of systemic juvenile idiopathic arthritis and macrophage activation syndrome","volume":"25","author":"Inoue","year":"2023","journal-title":"Arthritis Res Ther"},{"key":"2025062505515982000_CIT0073","first-page":"e8","article-title":"A xenograft model of macrophage activation syndrome amenable to anti-CD33 and anti\u2013IL-6R treatment","volume":"1","author":"Wunderlich","year":"8181","journal-title":"JCI Insight"},{"key":"2025062505515982000_CIT0074","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.rvsc.2020.12.003","article-title":"Pathology of macrophage activation syndrome in humanized NSGS mice","volume":"134","author":"Tarrant","year":"2021","journal-title":"Res Vet Sci"},{"key":"2025062505515982000_CIT0075","first-page":"4","article-title":"Graded defects in cytotoxicity determine severity of hemophagocytic lymphohistiocytosis in humans and mice","volume":"4","author":"Jessen","year":"2013","journal-title":"Front Immunol [Internet]"},{"key":"2025062505515982000_CIT0076","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1002\/eji.201948123","article-title":"Trigger-dependent differences determine therapeutic outcome in murine primary hemophagocytic lymphohistiocytosis","volume":"50","author":"Gather","year":"2020","journal-title":"Eur J Immunol"},{"key":"2025062505515982000_CIT0077","doi-asserted-by":"crossref","first-page":"e16085","DOI":"10.15252\/emmm.202216085","article-title":"Adoptive T cell therapy cures mice from active hemophagocytic lymphohistiocytosis (HLH)","volume":"14","author":"Wei\u00dfert","year":"2022","journal-title":"EMBO Mol Med"},{"key":"2025062505515982000_CIT0078","doi-asserted-by":"publisher","first-page":"e1002326","DOI":"10.1371\/journal.ppat.1002326","article-title":"Novel mouse xenograft models reveal a critical role of CD4+ T cells in the proliferation of ebv-infected T and NK cells","volume":"7","author":"Imadome","year":"2011","journal-title":"PLoS Pathog"},{"key":"2025062505515982000_CIT0079","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1182\/blood-2012-07-441139","article-title":"Hemophagocytic lymphohistiocytosis in syntaxin-11\u2013deficient mice: T-cell exhaustion limits fatal disease","volume":"121","author":"K\u00f6gl","year":"2013","journal-title":"Blood"},{"key":"2025062505515982000_CIT0080","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1007\/s10875-022-01289-3","article-title":"Human inborn errors of immunity: 2022 update on the classification from the international union of immunological societies expert committee","volume":"42","author":"Tangye","year":"2022","journal-title":"J Clin Immunol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cei\/advance-article-pdf\/doi\/10.1093\/cei\/uxaf036\/63393833\/uxaf036.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/219\/1\/uxaf036\/63393833\/uxaf036.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/219\/1\/uxaf036\/63393833\/uxaf036.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T05:52:11Z","timestamp":1750830731000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/doi\/10.1093\/cei\/uxaf036\/8152364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":80,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,21]]}},"URL":"https:\/\/doi.org\/10.1093\/cei\/uxaf036","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"uxaf036"}}