TGF-β inhibits Fas-mediated apoptosis of a follicular dendritic cell line by down-regulating the expression of Fas and caspase-8: Counteracting role of TGF-β on TNF sensitization of Fas-mediated apoptosis

Sun Mi Park, Sunshin Kim, Jin Suk Choi, Dae Young Hur, Wang Jae Lee, Myung Shik Lee, Jongseon Choe, Tae H. Lee

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Follicular dendritic cells (FDC) constitute the framework of germinal center (GC) in secondary lymphoid follicles, and the integrity of FDC networks is critically affected by cytokines present in the GC. We have previously shown that TNF promotes Fas-mediated apoptosis of HK cells, an established FDC-like cell line, by up-regulating Fas expression. However, in the developing GC, FDC death is not a hallmark of GC despite the presence of TNF and FasL. In this study, we report that TGF-β inhibits Fas-mediated apoptosis of HK cells by down-regulating the expression of surface Fas and caspase-8. The inhibitory effect of TGF-β can be observed when HK cells were simultaneously treated with TNF and TGF-β, indicating that TGF-β counteracts the effect of TNF in sensitizing cells to Fas-mediated apoptosis. Furthermore, the deprivation of TGF-β by injecting neutralizing TGF-β Abs to the SRBC-immunized mice resulted in the sporadic appearance of FDC undergoing apoptosis in the lymphoid follicles, suggesting that TGF-β functions as a naturally occurring inhibitor that rescues FDCs which are predisposed to apoptosis. Our study documents a novel function of TGF-β in the maintenance of FDC networks.

Original languageEnglish
Pages (from-to)6169-6175
Number of pages7
JournalJournal of Immunology
Issue number10
Publication statusPublished - 2005 May 15


All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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