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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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
Volume174
Issue number10
Publication statusPublished - 2005 May 15

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Follicular Dendritic Cells
Caspase 8
Germinal Center
Apoptosis
Cell Line
Cell Death
Maintenance
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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title = "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",
abstract = "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.",
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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. / Park, Sun Mi; Kim, Sunshin; Choi, Jin Suk; Hur, Dae Young; Lee, Wang Jae; Lee, Myung Shik; Choe, Jongseon; Lee, Tae H.

In: Journal of Immunology, Vol. 174, No. 10, 15.05.2005, p. 6169-6175.

Research output: Contribution to journalArticle

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AU - Kim, Sunshin

AU - Choi, Jin Suk

AU - Hur, Dae Young

AU - Lee, Wang Jae

AU - Lee, Myung Shik

AU - Choe, Jongseon

AU - Lee, Tae H.

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N2 - 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.

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