6533b831fe1ef96bd1299a72
RESEARCH PRODUCT
Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins
R De MariaAnn ZeunerLuigi RucoDiana Di LibertoAntonella StoppacciaroFelicia FarinaGiovanni ZummoMatilde TodaroLucia Ricci-vitianiGiorgio Stassisubject
Adultendocrine systemmedicine.medical_specialtyFas Ligand Proteinendocrine system diseasesCell SurvivalImmunologyCASP8 and FADD-Like Apoptosis Regulating ProteinThyroid Glandbcl-X ProteinApoptosisMice TransgenicIn Vitro TechniquesThyroiditisThyrotropin receptorMiceTh2 CellsSettore MED/04 - PATOLOGIA GENERALEInternal medicinemedicineImmunology and AllergyAnimalsHumansInterferon gammafas ReceptorInterleukin 4CaspaseMembrane GlycoproteinsbiologyThyroidIntracellular Signaling Peptides and ProteinsThyroiditis AutoimmuneT-Lymphocytes Helper-InducerMiddle AgedTh1 CellsFas receptormedicine.diseaseGraves DiseaseInterleukin 10medicine.anatomical_structureEndocrinologyProto-Oncogene Proteins c-bcl-2biology.proteinCytokinesCarrier Proteinsmedicine.drugdescription
After autoimmune inflammation, interactions between CD95 and its ligand (CD95L) mediate thyrocyte destruction in Hashimoto's thyroiditis (HT). Conversely, thyroid autoimmune processes that lead to Graves' disease (GD) result in autoantibody-mediated thyrotropin receptor stimulation without thyrocyte depletion. We found that GD thyrocytes expressed CD95 and CD95L in a similar manner to HT thyrocytes, but did not undergo CD95-induced apoptosis either in vivo or in vitro. This pattern was due to the differential production of TH1 and TH2 cytokines. Interferon gamma promoted caspase up-regulation and CD95-induced apoptosis in HT thyrocytes, whereas interleukin 4 and interleukin 10 protected GD thyrocytes by potent up-regulation of cFLIP and Bcl-xL, which prevented CD95-induced apoptosis in sensitized thyrocytes. Thus, modulation of apoptosis-related proteins by TH1 and TH2 cytokines controls thyrocyte survival in thyroid autoimmunity.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2000-01-01 |