Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts
Fiorini V, Hu B, Sun Y, Yu S, McGovern J, Gandhi S, Woo S, Turcotte-Foster S, Pivarnik T, Khan Z, Adams T, Herzog E, Kaminski N, Gulati M, Ryu C. Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts. CHEST Journal 2023, 165: 1174-1185. PMID: 37977267, PMCID: PMC11110677, DOI: 10.1016/j.chest.2023.11.020.Peer-Reviewed Original ResearchPatient-related outcome measuresToll-like receptor 9Fatigue Assessment ScalePlasma mtDNA concentrationsTLR9 activationSarcoidosis patientsMtDNA concentrationsMulti-organ sarcoidosisCommon chief complaintInnate immune activationNovel therapeutic strategiesDomains of fatigueSevere clinical phenotypePsychobiologic mechanismsSarcoidosis cohortScadding stageCorticosteroid useCytokine levelsExtrapulmonary diseaseProspective cohortFAS scoresPulmonary fibrosisChief complaintImmune activationPatient populationTLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance
Çakan E, Kioon M, Garcia-Carmona Y, Glauzy S, Oliver D, Yamakawa N, Loza A, Du Y, Schickel J, Boeckers J, Yang C, Baldo A, Ivashkiv L, Young R, Staudt L, Moody K, Nündel K, Marshak-Rothstein A, van der Made C, Hoischen A, Hayward A, Rossato M, Radstake T, Cunningham-Rundles C, Ryu C, Herzog E, Barrat F, Meffre E. TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance. Journal Of Experimental Medicine 2023, 220: e20230944. PMID: 37773045, PMCID: PMC10541333, DOI: 10.1084/jem.20230944.Peer-Reviewed Original ResearchConceptsCentral B cell toleranceB cell toleranceCell toleranceB cellsSystemic sclerosisTLR9 functionNovel therapeutic strategiesTLR9/MyD88Immature B cellsB cell receptorTolerogenic functionSSc patientsTLR9 expressionHumanized miceTLR9 responsesAutoreactive clonesTherapeutic strategiesChemokine CXCL4Cell receptorCXCL4Vivo productionTLR9MyD88ReceptorsCells