title: Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins.
abstract: 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.
authors: Department of Surgical, Anatomical and Oncological Sciences, Human Anatomy Section, University of Palermo, Italy.
authors: G
authors: G
authors: Stassi
authors: D
authors: D
authors: Di Liberto
authors: M
authors: M
authors: Todaro
authors: A
authors: A
authors: Zeuner
authors: L
authors: L
authors: Ricci-Vitiani
authors: A
authors: A
authors: Stoppacciaro
authors: L
authors: L
authors: Ruco
authors: F
authors: F
authors: Farina
authors: G
authors: G
authors: Zummo
authors: R
authors: R
authors: De Maria
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism*; D053222:Fas Ligand Protein; D006111:Graves Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051020:bcl-X Protein; D019014:fas Receptor / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; C506387:Cflar protein, mouse; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor