2024
NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7
Gordon R, Cosgrove H, Marinov A, Gingras S, Tilstra J, Campbell A, Bastacky S, Kashgarian M, Perl A, Nickerson K, Shlomchik M. NADPH oxidase in B cells and macrophages protects against murine lupus by regulation of TLR7. JCI Insight 2024, 9: e178563. PMID: 39042716, PMCID: PMC11343599, DOI: 10.1172/jci.insight.178563.Peer-Reviewed Original ResearchSystemic lupus erythematosusB cellsRegulation of TLR7Cell lineagesNADPH oxidaseHematopoietic cell lineagesNF-kB signalingSLE pathologyNOX2 deficiencyMyeloid compartmentMurine lupusLupus nephritisLupus erythematosusTLR7 signalingGlobal deletionInterstitial nephritisImmunomodulatory effectsGlobal knockoutConditional knockoutCYBBNOX2NephritisKnockoutTLR7Chimera approach
2022
A Human MSH6 Germline Variant Associated With Systemic Lupus Erythematosus Induces Lupus‐like Disease in Mice
Meas R, Nititham J, Taylor KE, Maher S, Clairmont K, Carufe KEW, Kashgarian M, Nottoli T, Cheong A, Nagel ZD, Gaffney PM, Criswell LA, Sweasy JB. A Human MSH6 Germline Variant Associated With Systemic Lupus Erythematosus Induces Lupus‐like Disease in Mice. ACR Open Rheumatology 2022, 4: 760-770. PMID: 35708944, PMCID: PMC9469486, DOI: 10.1002/acr2.11471.Peer-Reviewed Original ResearchSystemic lupus erythematosusAntinuclear antibodiesMSH6 variantsLupus erythematosusMSH6 mutationsMouse modelSingle nucleotide polymorphismsDevelopment of SLELevel of ANAInfiltration of CD68Lupus-like diseaseInflammatory lung diseasesLung alveolar spacesRepair genesMismatch repair genesLung diseaseHealthy controlsPeyer's patchesWildtype miceAlveolar spaceCRISPR/Cas9 gene targetingSomatic hypermutation frequenciesAutoimmune phenotypeMiceDifferent mismatch repair genes
2020
B cell-intrinsic TLR9 expression is protective in murine lupus
Tilstra JS, John S, Gordon RA, Leibler C, Kashgarian M, Bastacky S, Nickerson KM, Shlomchik MJ. B cell-intrinsic TLR9 expression is protective in murine lupus. Journal Of Clinical Investigation 2020, 130: 3172-3187. PMID: 32191633, PMCID: PMC7260024, DOI: 10.1172/jci132328.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Systemic lupus erythematosusTLR9 deficiencyTLR9 expressionDendritic cellsB cellsPlasmacytoid dendritic cellsAnti-nucleosome antibodiesLupus erythematosusAutoantibody productionMurine lupusSLE pathogenesisTLR9 signalsReceptor 9Cell type-specific effectsType-specific effectsDisease pathogenesisTherapeutic potentialSelective deletionDiseaseNonredundant roleNephritisLupusPathogenesisDeficiency
2011
A Small-Molecule Macrophage Migration Inhibitory Factor Antagonist Protects against Glomerulonephritis in Lupus-Prone NZB/NZW F1 and MRL/lpr Mice
Leng L, Chen L, Fan J, Greven D, Arjona A, Du X, Austin D, Kashgarian M, Yin Z, Huang XR, Lan HY, Lolis E, Nikolic-Paterson D, Bucala R. A Small-Molecule Macrophage Migration Inhibitory Factor Antagonist Protects against Glomerulonephritis in Lupus-Prone NZB/NZW F1 and MRL/lpr Mice. The Journal Of Immunology 2011, 186: 527-538. PMID: 21106847, PMCID: PMC3124407, DOI: 10.4049/jimmunol.1001767.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell Migration InhibitionFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGlomerulonephritisHumansIntramolecular OxidoreductasesIsoxazolesLupus Erythematosus, SystemicMacrophage Migration-Inhibitory FactorsMiceMice, Inbred MRL lprMice, Inbred NZBMice, KnockoutMolecular Sequence DataRandom AllocationReceptors, ImmunologicConceptsMacrophage migration inhibitory factorMRL/lpr miceNZB/NZW F1Systemic lupus erythematosusMigration inhibitory factorLupus erythematosusLpr miceDihydro-5-isoxazole acetic acid methyl esterHigh-expression MIF allelesInhibitory factorExcessive proinflammatory responsesRetention of monocytesEnd-organ injuryEnd-organ damageProinflammatory cytokine productionDifferent autoimmune diseasesB cell activationMIF antagonismMIF antagonistAutoantibody productionChemokine expressionProinflammatory cytokinesAutoimmune diseasesCytokine productionMIF alleles
2010
Dendritic Cells in Lupus Are Not Required for Activation of T and B Cells but Promote Their Expansion, Resulting in Tissue Damage
Teichmann LL, Ols ML, Kashgarian M, Reizis B, Kaplan DH, Shlomchik MJ. Dendritic Cells in Lupus Are Not Required for Activation of T and B Cells but Promote Their Expansion, Resulting in Tissue Damage. Immunity 2010, 33: 967-978. PMID: 21167752, PMCID: PMC3010763, DOI: 10.1016/j.immuni.2010.11.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesBlood Component RemovalB-LymphocytesCell DifferentiationCell MovementDendritic CellsDisease Models, AnimalHumansImmunoglobulin Class SwitchingInterferon-gammaLupus Erythematosus, SystemicLymphocyte ActivationMiceMice, Inbred C57BLMice, Inbred MRL lprT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsDendritic cellsAdaptive immune responsesMurine lupusImmune responseAbsence of DCsEffects of DCsSystemic lupus erythematosusSerum immunoglobulin concentrationsPotential therapeutic targetLupus erythematosusInterstitial infiltratesAutoimmune disordersHumoral responseAutoantibody concentrationsPlasmablast numbersImmunoglobulin concentrationsTherapeutic targetB cellsTissue damageLupusCell numberCellsInitial activationComplex roleActivation
1989
The Clinical and Renal Biopsy Predictors of Long-term Outcome in Lupus Nephritis: A Study of 87 Patients and Review of the Literature
ESDAILE J, LEVINTON C, FEDERGREEN W, HAYSLETT J, KASHGARIAN M. The Clinical and Renal Biopsy Predictors of Long-term Outcome in Lupus Nephritis: A Study of 87 Patients and Review of the Literature. QJM 1989, 72: 779-833. DOI: 10.1093/oxfordjournals.qjmed.a068371.Peer-Reviewed Original ResearchDuration of renal diseasePresence of vasculitisLong-term outcomesLupus nephritisRenal diseaseRenal insufficiencyRenal failurePrognostic markerClinical modelMarker of immunological activityRenal systemic lupus erythematosusPredictor of long-term outcomeMarkers of disease severityUrinary excretion of proteinNon-renal SLEImmunologic disease activitySystemic lupus erythematosusPredictors of fatalityExcretion of proteinRenal severityConsecutive patientsRenal outcomesChronicity indexBiopsy variablesSerum creatinineThe clinical and renal biopsy predictors of long-term outcome in lupus nephritis: a study of 87 patients and review of the literature.
Esdaile J, Levinton C, Federgreen W, Hayslett J, Kashgarian M. The clinical and renal biopsy predictors of long-term outcome in lupus nephritis: a study of 87 patients and review of the literature. QJM 1989, 72: 779-833. PMID: 2694209.Peer-Reviewed Original ResearchConceptsPresence of vasculitisLong-term outcomesLupus nephritisRenal diseaseClinical modelRenal insufficiencyRenal failurePrognostic markerRelevant long-term outcomesRenal systemic lupus erythematosusImmunologic disease activityNon-renal SLESystemic lupus erythematosusImportant prognostic markerChronicity indexRenal outcomesRenal severityDisease activityNew predictive informationSerum creatinineConsecutive patientsLupus erythematosusPrognostic factorsRenal biopsyComorbid conditions