Abundant c-Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein expression determines resistance of T helper 17 cells to activation-induced cell death.
Activation-induced cell death (AICD) plays an important role in peripheral T-cell tolerance. AICD in CD4 T helper (Th) cells, including Th1 and Th2 effectors, has been extensively studied. Recently, interleukin-17-producing CD4(+) T cells (Th17 cells) have been identified as a unique Th subset, but their susceptibility to AICD and the underlying molecular mechanisms have not been defined. In this study, we found that Th17 cells were significantly less susceptible to AICD than Th1 cells, and Th17 cell resistance to AICD is due to the high levels of c-Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein preventing Fas-mediated apoptosis. The resistance of Th17 cells to AICD reveals a novel mechanism to explain the high pathogenicity of Th17 cells in autoimmune diseases, and may also provide a rationale to generate tumor-specific Th17 cells for adoptive immunotherapy.
Departments of Immunology and Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612-9497, USA.
Yu
Y
Yu
Cristina
C
Iclozan
Tomohide
T
Yamazaki
Xuexian
X
Yang
Claudio
C
Anasetti
Chen
C
Dong
Xue-Zhong
XZ
Yu
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis / Q000502:physiology*; D002478:Cells, Cultured / Q000276:immunology; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000502:physiology; D017930:Genes, Reporter; D007108:Immune Tolerance / Q000502:physiology*; D007114:Immunization; D020381:Interleukin-17 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011828:Radiation Chimera; D013047:Specific Pathogen-Free Organisms; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D051020:bcl-X Protein / Q000502:physiology
C494812:Bcl2l1 protein, mouse; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506387:Cflar protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D020381:Interleukin-17; D034741:RNA, Small Interfering; D051020:bcl-X Protein; D010047:Ovalbumin