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Citations to this article

Repeated TLR9 stimulation results in macrophage activation syndrome–like disease in mice
Edward M. Behrens, … , Taku Kambayashi, Gary A. Koretzky
Edward M. Behrens, … , Taku Kambayashi, Gary A. Koretzky
Published May 16, 2011
Citation Information: J Clin Invest. 2011;121(6):2264-2277. https://doi.org/10.1172/JCI43157.
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Research Article Immunology Article has an altmetric score of 15

Repeated TLR9 stimulation results in macrophage activation syndrome–like disease in mice

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Abstract

Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are 2 similar diseases characterized by a cytokine storm, overwhelming inflammation, multiorgan dysfunction, and death. Animal models of HLH suggest that disease is driven by IFN-γ produced by CD8+ lymphocytes stimulated by persistent antigen exposure. In these models and patients with “primary” HLH, the antigen persists due to genetic defects, resulting in ineffective cytotoxic responses by CD8+ T cells and poor pathogen clearance. However, infectious triggers are often not identified in patients with MAS, and some patients with HLH or MAS lack defects in cytotoxic T cell killing. Herein, we show that repeated stimulation of TLR9 produced an HLH/MAS-like syndrome on a normal genetic background, without exogenous antigen. Like previous HLH models, TLR9-induced MAS was IFN-γ dependent; however, unlike other models, disease did not require lymphocytes. We further showed that IL-10 played a protective role in this model and that blocking IL-10 signaling led to the development of hemophagocytosis. IL-10 may therefore be an important target for the development of effective therapeutics for MAS. Our data provide insight into MAS-like syndromes in patients with inflammatory diseases in which there is chronic innate immune activation but no genetic defects in cytotoxic cell function.

Authors

Edward M. Behrens, Scott W. Canna, Katharine Slade, Sheila Rao, Portia A. Kreiger, Michele Paessler, Taku Kambayashi, Gary A. Koretzky

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Frontiers in immunology 2019
Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome
O Halyabar, MH Chang, ML Schoettler, MA Schwartz, EH Baris, LA Benson, CM Biggs, M Gorman, L Lehmann, MS Lo, PA Nigrovic, CD Platt, GP Priebe, J Rowe, RP Sundel, NK Surana, KG Weinacht, A Mann, JC Yuen, P Meleedy-Rey, A Starmer, T Banerjee, F Dedeoglu, BA Degar, MM Hazen, LA Henderson
Pediatric Rheumatology 2019
Mechanisms of Action of Ruxolitinib in Murine Models of Hemophagocytic Lymphohistiocytosis
S Albeituni, KC Verbist, PE Tedrick, H Tillman, J Picarsic, R Bassett, KE Nichols
Blood 2019
A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation
SJ Tavernier, V Athanasopoulos, P Verloo, G Behrens, J Staal, DJ Bogaert, L Naesens, MD Bruyne, SV Gassen, E Parthoens, J Ellyard, J Cappello, LX Morris, HV Gorp, GV Isterdael, Y Saeys, M Lamkanfi, P Schelstraete, J Dehoorne, V Bordon, RV Coster, BN Lambrecht, B Menten, R Beyaert, CG Vinuesa, V Heissmeyer, M Dullaers, F Haerynck
Nature Communications 2019
Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis
PY Lee, GS Schulert, SW Canna, Y Huang, J Sundel, Y Li, KJ Hoyt, RB Blaustein, A Wactor, T Do, O Halyabar, MH Chang, F Dedeoglu, SM Case, E Meidan, MS Lo, RP Sundel, ET Richardson, JW Newburger, MS Hershfield, MB Son, LA Henderson, PA Nigrovic
Annals of the rheumatic diseases 2019
Synergistic TLR/IFNα/β-Signaling Facilitates Escape of IL-18 Expression from Endotoxin Tolerance
E Verweyen, D Holzinger, T Weinhage, C Hinze, H Wittkowski, P Pickkers, S Albeituni, K Verbist, KE Nichols, G Schulert, A Grom, D Foell, C Kessel
American journal of respiratory and critical care medicine 2019
Diacylglycerol Kinase ζ Regulates Macrophage Responses in Juvenile Arthritis and Cytokine Storm Syndrome Mouse Models
S Mahajan, ED Mellins, R Faccio
Journal of immunology (Baltimore, Md. : 1950) 2019
Cloak and dagger ‐ secondary hemophygocytic lymphohistiocytosis caused by intravenous autoinfection
A Pircher, S Koeck, J Schatzlmayr, A Finkenstedt, M Nairz, D Wanner, A Griesmacher, H Tilg, D Wolf, H Zoller
American Journal of Hematology 2019
Emapalumab for the treatment of relapsed/refractory hemophagocytic lymphohistiocytosis
M Vallurupalli, N Berliner
Blood 2019
Senescence-accelerated mice (SAMP1/TA-1) treated repeatedly with lipopolysaccharide develop a condition that resembles hemophagocytic lymphohistiocytosis
I Tsuboi, T Harada, Y Hirabayashi, S Aizawa
Haematologica 2019
Integrin αDβ2 (CD11d/CD18) Modulates Leukocyte Accumulation, Pathogen Clearance, and Pyroptosis in Experimental Salmonella Typhimurium Infection
D de Oliveira Nascimento, A Vieira-de-Abreu, AF Arcanjo, PT Bozza, GA Zimmerman, HC Castro-Faria-Neto
Frontiers in immunology 2018
Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome
ES Weiss, C Girard-Guyonvarc'h, D Holzinger, AA de Jesus, Z Tariq, J Picarsic, EJ Schiffrin, D Foell, AA Grom, S Ammann, S Ehl, T Hoshino, R Goldbach-Mansky, C Gabay, SW Canna
Blood 2018
Lymphocyte-independent pathways underlie the pathogenesis of murine cytomegalovirus-associated secondary haemophagocytic lymphohistiocytosis: Non-adaptive immune pathogenesis in HLH
E Brisse, M Imbrechts, T Mitera, J Vandenhaute, N Berghmans, L Boon, C Wouters, R Snoeck, G Andrei, P Matthys
Clinical & Experimental Immunology 2018
Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab
A Hantel, B Gabster, JX Cheng, H Golomb, TF Gajewski
Journal for ImmunoTherapy of Cancer 2018
High Mobility Group Box 1 Influences HSV1716 Spread and Acts as an Adjuvant to Chemotherapy
L Sprague, J Lee, B Hutzen, PY Wang, CY Chen, J Conner, L Braidwood, K Cassady, T Cripe
Viruses 2018
Please stand by: how oncolytic viruses impact bystander cells
L Sprague, L Braidwood, J Conner, KA Cassady, F Benencia, TP Cripe
Future Virology 2018
A prospective quality improvement initiative in adult hemophagocytic lymphohistiocytosis to improve testing and a framework to facilitate trigger identification and mitigate hemorrhage from retrospective analysis:
SA Merrill, R Naik, MB Streiff, S Shanbhag, S Lanzkron, EM Braunstein, AM Moliterno, RA Brodsky
Medicine 2018
Adult-Onset Still’s Disease and Macrophage-Activating Syndrome Progressing to Lymphoma: A Clinical Pathology Conference Held by the Division of Rheumatology at Hospital for Special Surgery
B Mehta, S Kasturi, J Teruya-Feldstein, S Horwitz, AR Bass, D Erkan
HSS Journal 2018
Convergent pathways of the hyperferritinemic syndromes
GS Schulert, SW Canna
International Immunology 2018
PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal nucleic-acid sensing
AL Gavin, D Huang, C Huber, A Mårtensson, V Tardif, PD Skog, TR Blane, TC Thinnes, K Osborn, HS Chong, F Kargaran, P Kimm, A Zeitjian, RL Sielski, M Briggs, SR Schulz, A Zarpellon, B Cravatt, ES Pang, J Teijaro, JC de la Torre, M OKeeffe, H Hochrein, M Damme, L Teyton, BR Lawson, D Nemazee
Nature Immunology 2018
Understanding Disseminated Intravascular Coagulation and Hepatobiliary Dysfunction Multiple Organ Failure in Hyperferritinemic Critical Illness*:
JA Carcillo, B Shakoory, D Simon, K Kernan
Pediatric Critical Care Medicine 2018
Interferon-γ-Mediated Immunopathology Potentiated by Toll-Like Receptor 9 Activation in a Murine Model of Macrophage Activation Syndrome
LK Weaver, N Chu, EM Behrens
Arthritis & Rheumatology 2018
Secondary Hemophagocytic Lymphohistiocytosis, Macrophage Activation Syndrome, and Hyperferritinemic Sepsis-Induced Multiple-Organ Dysfunction Syndrome in the Pediatric ICU
Carcillo JA, Shakoory B, Castillo L
Pediatric Critical Care 2018
Macrophage Activation Syndrome
Eloseily EM, Cron RQ
2018
Diagnosis, Treatment, and Management of Hemophagocytic Lymphohistiocytosis in the Critical Care Unit
Hines M, Bhatt N, Talano JA
2018
HIF1A is a critical downstream mediator for hemophagocytic lymphohistiocytosis
R Huang, Y Hayashi, X Yan, J Bu, J Wang, Y Zhang, Y Zhou, Y Tang, L Wu, Z Xu, X Liu, Q Wang, J Zhou, Z Xiao, JP Bridges, RA Marsh, K Zhang, MB Jordan, Y Li, G Huang
Haematologica 2017
Macrophages and the Recovery from Acute and Chronic Inflammation
K Hamidzadeh, SM Christensen, E Dalby, P Chandrasekaran, DM Mosser
Annual Review of Physiology 2017
A Personalized Diagnostic and Treatment Approach for Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Adults
B Kumar, S Aleem, H Saleh, J Petts, ZK Ballas
Journal of Clinical Immunology 2017
Macrophages: Key orchestrators of a tumor microenvironment defined by therapeutic resistance
KB Long, AI Collier, GL Beatty
Molecular Immunology 2017
Hemophagocytic lymphohistiocytosis in an adult kidney transplant recipient successfully treated by plasmapheresis: A case report and review of the literature
C Nusshag, C Morath, M Zeier, MA Weigand, U Merle, T Brenner
Medicine 2017
Proliferation through activation: hemophagocytic lymphohistiocytosis in hematologic malignancy
EJ Vick, K Patel, P Prouet, MG Martin
Blood Advances 2017
Macrophage Activation Syndrome: different mechanisms leading to a one clinical syndrome
C Bracaglia, G Prencipe, FD Benedetti
Pediatric Rheumatology 2017
Pathophysiology of Pediatric Multiple Organ Dysfunction Syndrome:
JA Carcillo, B Podd, R Aneja, SL Weiss, MW Hall, TT Cornell, TP Shanley, LA Doughty, TC Nguyen
Pediatric Critical Care Medicine 2017
Weathering the Storm: Improving Therapeutic Interventions for Cytokine Storm Syndromes by Targeting Disease Pathogenesis
LK Weaver, EM Behrens
Current Treatment Options in Rheumatology 2017
Hyperferritinemia and inflammation
KF Kernan, JA Carcillo
International Immunology 2017
Induction of Live Cell Phagocytosis by a Specific Combination of Inflammatory Stimuli
T Ishidome, T Yoshida, R Hanayama
EBioMedicine 2017
How Viruses Contribute to the Pathogenesis of Hemophagocytic Lymphohistiocytosis
E Brisse, CH Wouters, G Andrei, P Matthys
Frontiers in immunology 2017
Interleukin-18: Biological properties and role in disease pathogenesis
G Kaplanski
Immunological Reviews 2017
Lytic viral replication and immunopathology in a cytomegalovirus-induced mouse model of secondary hemophagocytic lymphohistiocytosis
E Brisse, M Imbrechts, T Mitera, J Vandenhaute, CH Wouters, R Snoeck, G Andrei, P Matthys
Virology Journal 2017
[Hemophagocytic lymphohistiocytosis: advances on etiologies, diagnosis and treatment]
D J Wang, H X Qiu
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 2017
Diseases Primarily Affecting the Reproductive System
Veterinary Medicine 2017
A xenograft model of macrophage activation syndrome amenable to anti-CD33 and anti-IL-6R treatment
Mark Wunderlich, Courtney Stockman, Mahima Devarajan, Navin Ravishanakar, Christina Sexton, Ashish Kumar, Benjamin Mizukawa, James Mulloy
JCI Insight 2016
IDO1 Deficiency Does Not Affect Disease in Mouse Models of Systemic Juvenile Idiopathic Arthritis and Secondary Hemophagocytic Lymphohistiocytosis
K Put, E Brisse, A Avau, M Imbrechts, T Mitera, R Janssens, P Proost, F Fallarino, CH Wouters, P Matthys, L Graca
PloS one 2016
Hämophagozytische Lymphohistiozytose: Diagnostische Herausforderung auf der ITS
G Lachmann, PL Rosée, T Schenk, FM Brunkhorst, C Spies
Der Anaesthesist 2016
Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis
R Das, P Guan, L Sprague, K Verbist, P Tedrick, QA An, C Cheng, M Kurachi, R Levine, EJ Wherry, SW Canna, EM Behrens, KE Nichols
Blood 2016
Macrophage activation syndrome in the era of biologic therapy
AA Grom, AC Horne, FD Benedetti
Nature Reviews Rheumatology 2016
TLR9-mediated inflammation drives a Ccr2-independent peripheral monocytosis through enhanced extramedullary monocytopoiesis
LK Weaver, N Chu, EM Behrens
Proceedings of the National Academy of Sciences 2016
Macrophage activation syndrome in children with systemic juvenile idiopathic arthritis and systemic lupus erythematosus
S Aytaç, ED Batu, Ş Ünal, Y Bilginer, M Çetin, M Tuncer, F Gümrük, S Özen
Rheumatology International 2016
Hemophagocytic lymphohistiocytosis: an update for nephrologists
EJ Filippone, JL Farber
International Urology and Nephrology 2016
Use of a mouse model to identify a blood biomarker for IFNγ activity in pediatric secondary hemophagocytic lymphohistiocytosis
V Buatois, L Chatel, L Cons, S Lory, F Richard, F Guilhot, Z Johnson, C Bracaglia, FD Benedetti, C Min, MH Kosco-Vilbois, WG Ferlin
Translational Research 2016
Proinflammatory Stimulation of Toll-Like Receptor 9 with High Dose CpG ODN 1826 Impairs Endothelial Regeneration and Promotes Atherosclerosis in Mice
AO Krogmann, E Lüsebrink, M Steinmetz, T Asdonk, C Lahrmann, D Lütjohann, G Nickenig, S Zimmer, LM Sly
PloS one 2016
Distinct immunological activation profiles of dSLIM® and ProMune® depend on their different structural context: dSLIM® versus ProMune®
K Kapp, J Schneider, L Schneider, N Gollinge, S Jänsch, M Schroff, B Wittig, C Kleuss
Immunity, Inflammation and Disease 2016
IL-10 distinguishes a unique population of activated, effector-like CD8 + T cells in murine acute liver inflammation
JE Rood, SW Canna, LK Weaver, JW Tobias, EM Behrens
Journal of leukocyte biology 2016
Salmonella Infection Enhances Erythropoietin Production by the Kidney and Liver, Which Correlates with Elevated Bacterial Burdens
LX Li, JM Benoun, K Weiskopf, KC Garcia, SJ McSorley, VB Young
Infection and immunity 2016
From bench to bedside and back again: translational research in autoinflammation
D Holzinger, C Kessel, A Omenetti, M Gattorno
Nature Reviews Rheumatology 2015
Therapeutic Potential of Interferon-γ and Its Antagonists in Autoinflammation: Lessons from Murine Models of Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome
A Avau, P Matthys
Pharmaceuticals (Basel, Switzerland) 2015
Cytotoxic granule secretion by lymphocytes and its link to immune homeostasis
GS saint Basile, FE Sepulveda, S Maschalidi, A Fischer
F1000Research 2015
A Novel Model for IFN- -Mediated Autoinflammatory Syndromes
RL Reinhardt, HE Liang, K Bao, AE Price, M Mohrs, BL Kelly, RM Locksley
Journal of immunology (Baltimore, Md. : 1950) 2015
Pathogenesis of Macrophage Activation Syndrome and Potential for Cytokine- Directed Therapies
GS Schulert, AA Grom
Annual Review of Medicine 2015
Toll-like receptor 9 and interferon-γ receptor signaling suppress the B-cell fate of uncommitted progenitors in mice: Cellular immune response
SR Baratono, N Chu, LP Richman, EM Behrens
European Journal of Immunology 2015
Molecular Mechanisms in Genetically Defined Autoinflammatory Diseases: Disorders of Amplified Danger Signaling*
AA de Jesus, SW Canna, Y Liu, R Goldbach-Mansky
Annual Review of Immunology 2015
How We Manage Hyperferritinemic Sepsis-Related Multiple Organ Dysfunction Syndrome/Macrophage Activation Syndrome/Secondary Hemophagocytic Lymphohistiocytosis Histiocytosis*:
JA Carcillo, DW Simon, BS Podd
Pediatric Critical Care Medicine 2015
Increased Ferroportin-1 Expression and Rapid Splenic Iron Loss Occur with Anemia Caused by Salmonella enterica Serovar Typhimurium Infection in Mice
DE Brown, HJ Nick, MW McCoy, SM Moreland, AM Stepanek, R Benik, KE O'Connell, MC Pilonieta, TA Nagy, CS Detweiler, AJ Bäumler
Infection and immunity 2015
Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice
Y Dhondup, I Sjaastad, H Scott, Ø Sandanger, L Zhang, SB Haugstad, JM Aronsen, T Ranheim, SD Holmen, K Alfsnes, MS Ahmed, H Attramadal, L Gullestad, P Aukrust, G Christensen, A Yndestad, LE Vinge, J Calvert
PloS one 2015
An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome)
H Esmaili, E Mostafidi, B Mehramuz, M Ardalan, M Mohajel-Shoja
Journal of Nephropathology 2015
Novel Insights into Interleukin 6 (IL-6) Cis- and Trans-signaling Pathways by Differentially Manipulating the Assembly of the IL-6 Signaling Complex
M Lacroix, F Rousseau, F Guilhot, P Malinge, G Magistrelli, S Herren, SA Jones, GW Jones, J Scheller, R Lissilaa, M Kosco-Vilbois, Z Johnson, V Buatois, W Ferlin
The Journal of biological chemistry 2015
Hyperinflammation, rather than hemophagocytosis, is the common link between macrophage activation syndrome and hemophagocytic lymphohistiocytosis:
LK Weaver, EM Behrens
Current Opinion in Rheumatology 2014
Safety, tolerability, and biomarkers of the treatment of mice with aerosolized Toll-like receptor ligands
VY Alfaro, DL Goldblatt, GR Valverde, MF Munsell, LJ Quinton, AK Walker, R Dantzer, A Varadhachary, BL Scott, SE Evans, MJ Tuvim, BF Dickey
Frontiers in pharmacology 2014
Genetic Defects in Cytolysis in Macrophage Activation Syndrome
M Zhang, EM Behrens, TP Atkinson, B Shakoory, AA Grom, RQ Cron
Current Rheumatology Reports 2014
Macrophage activation syndrome and cytokine-directed therapies
GS Schulert, AA Grom
Best Practice & Research Clinical Rheumatology 2014
Editorial: Interferon-γ: Friend or Foe in Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease?: Editorial
SW Canna
Arthritis & Rheumatology 2014
Plasma Exchange, Methylprednisolone, IV Immune Globulin, and Now Anakinra Support Continued PICU Equipoise in Management of Hyperferritinemia-Associated Sepsis/Multiple Organ Dysfunction Syndrome/Macrophage Activation Syndrome/Secondary Hemophagocytic Lymphohistiocytosis Syndrome*:
DW Simon, R Aneja, JA Carcillo, ES Halstead
Pediatric Critical Care Medicine 2014
Salmonella enterica Infection Stimulates Macrophages to Hemophagocytose
MC Pilonieta, SM Moreland, CN English, CS Detweiler
mBio 2014
Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function
R Markwart, SA Condotta, RP Requardt, F Borken, K Schubert, C Weigel, M Bauer, TS Griffith, M Förster, FM Brunkhorst, VP Badovinac, I Rubio, PA Efron
PloS one 2014
Transcriptional profile in afferent lymph cells following vaccination with liposomes incorporating CpG
MR Neeland, MJ Elhay, DR Powell, FJ Rossello, EN Meeusen, MJ de Veer
Immunology 2014
Hemophagocytic Lymphohistiocytosis Syndromes
Standage SW, Filipovich AH
Pediatric Critical Care Medicine 2014
Adoptive T Cell Transfer for Cancer Immunotherapy in the Era of Synthetic Biology
M Kalos, CH June
Immunity 2013
Experimental infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus
B Guo, KM Lager, JN Henningson, LC Miller, SN Schlink, MA Kappes, ME Kehrli, SL Brockmeier, TL Nicholson, HC Yang, KS Faaberg
Virology 2013
Interferon-γ Mediates Anemia but Is Dispensable for Fulminant Toll-like Receptor 9-Induced Macrophage Activation Syndrome and Hemophagocytosis in Mice: IFN-γ-Independent MAS and Hemophagocytosis
SW Canna, J Wrobel, N Chu, PA Kreiger, M Paessler, EM Behrens
Arthritis & Rheumatism 2013
Increased ribonuclease expression reduces inflammation and prolongs survival in TLR7 transgenic mice
X Sun, A Wiedeman, N Agrawal, TH Teal, L Tanaka, KL Hudkins, CE Alpers, S Bolland, MB Buechler, JA Hamerman, JA Ledbetter, D Liggitt, KB Elkon
Journal of immunology (Baltimore, Md. : 1950) 2013
Chimeric antigen receptor-modified T cells for acute lymphoid leukemia
SA Grupp, M Kalos, D Barrett, R Aplenc, DL Porter, SR Rheingold, DT Teachey, A Chew, B Hauck, JF Wright, MC Milone, BL Levine, CH June
Boston Medical and Surgical Journal 2013
Pro-inflammatory action of Candida albicans DNA in zymosan-induced arthritis
P Dimitrova, S Danova, N Ivanovska
Inflammation Research 2012
Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis
SF Bode, K Lehmberg, A Maul-Pavicic, T Vraetz, G Janka, UZ Stadt, S Ehl
Arthritis Research & Therapy 2012
Not all hemophagocytes are created equally: appreciating the heterogeneity of the hemophagocytic syndromes
SW Canna, EM Behrens
Current Opinion in Rheumatology 2012
Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment?
D Demirkol, D Yildizdas, B Bayrakci, B Karapinar, T Kendirli, TF Koroglu, O Dursun, N Erkek, H Gedik, A Citak, S Kesici, M Karabocuoglu, JA Carcillo
Critical Care 2012
Making Sense of the Cytokine Storm: A Conceptual Framework for Understanding, Diagnosing, and Treating Hemophagocytic Syndromes
SW Canna, EM Behrens
Pediatric Clinics of North America 2012
Transmembrane Mutations in Toll-like Receptor 9 Bypass the Requirement for Ectodomain Proteolysis and Induce Fatal Inflammation
ML Mouchess, N Arpaia, G Souza, R Barbalat, SE Ewald, L Lau, GM Barton
Immunity 2011
Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions
ED Mellins, C Macaubas, AA Grom
Nature Reviews Rheumatology 2011

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