Targeted disruption of Traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation

H. Nakano; S. Sakon; H. Koseki; T. Takemori; K. Tada; M. Matsumoto; E. Munechika; T. Sakai; T. Shirasawa; H. Akiba; T. Kobata; S. M. Santee; C. F. Ware; P. D. Rennert; M. Taniguchi; H. Yagita; K. Okumura

doi:10.1073/pnas.96.17.9803

Targeted disruption of Traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation

H. Nakano, S. Sakon, H. Koseki, T. Takemori, K. Tada, M. Matsumoto, E. Munechika, T. Sakai, T. Shirasawa, H. Akiba, T. Kobata, S. M. Santee, C. F. Ware, P. D. Rennert, M. Taniguchi, H. Yagita, K. Okumura

Research Center for Transomics Medicine

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157 Citations (Scopus)

Abstract

TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-κB and c-Jun NH₂-terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-β receptor. To investigate the functional role of TRAF5 in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-κB or c-Jun NH₂-terminal kinase/stress-activated protein kinase by tumor necrosis factor, CD27, and CD40 was not abrogated in traf5(-/-) mice. However, traf5(-/-) B cells showed defects in proliferation and up-regulation of various surface molecules, including CD23, CD54, CD80, CD86, and Fas in response to CD40 stimulation. Moreover, in vitro Ig production of traf5(-/-) B cells stimulated with anti-CD40 plus IL-4 was reduced substantially. CD27-mediated costimulatory signal also was impaired in traf5(-/-) T cells. Collectively, these results demonstrate that TRAF5 is involved in CD40- and CD27-mediated signalling.

Original language	English
Pages (from-to)	9803-9808
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	96
Issue number	17
DOIs	https://doi.org/10.1073/pnas.96.17.9803
Publication status	Published - Aug 17 1999

All Science Journal Classification (ASJC) codes

General

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Nakano, H., Sakon, S., Koseki, H., Takemori, T., Tada, K., Matsumoto, M., Munechika, E., Sakai, T., Shirasawa, T., Akiba, H., Kobata, T., Santee, S. M., Ware, C. F., Rennert, P. D., Taniguchi, M., Yagita, H., & Okumura, K. (1999). Targeted disruption of Traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation. Proceedings of the National Academy of Sciences of the United States of America, 96(17), 9803-9808. https://doi.org/10.1073/pnas.96.17.9803

Targeted disruption of Traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation. / Nakano, H.; Sakon, S.; Koseki, H.; Takemori, T.; Tada, K.; Matsumoto, M.; Munechika, E.; Sakai, T.; Shirasawa, T.; Akiba, H.; Kobata, T.; Santee, S. M.; Ware, C. F.; Rennert, P. D.; Taniguchi, M.; Yagita, H.; Okumura, K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 17, 17.08.1999, p. 9803-9808.

Research output: Contribution to journal › Article

Nakano, H, Sakon, S, Koseki, H, Takemori, T, Tada, K, Matsumoto, M, Munechika, E, Sakai, T, Shirasawa, T, Akiba, H, Kobata, T, Santee, SM, Ware, CF, Rennert, PD, Taniguchi, M, Yagita, H & Okumura, K 1999, 'Targeted disruption of Traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation', Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 17, pp. 9803-9808. https://doi.org/10.1073/pnas.96.17.9803

Nakano, H. ; Sakon, S. ; Koseki, H. ; Takemori, T. ; Tada, K. ; Matsumoto, M. ; Munechika, E. ; Sakai, T. ; Shirasawa, T. ; Akiba, H. ; Kobata, T. ; Santee, S. M. ; Ware, C. F. ; Rennert, P. D. ; Taniguchi, M. ; Yagita, H. ; Okumura, K. / Targeted disruption of Traf5 gene causes defects in CD40- and CD27- mediated lymphocyte activation. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 17. pp. 9803-9808.

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abstract = "TRAF5 [tumor necrosis factor (TNF) receptor-associated factor 5] is implicated in NF-κB and c-Jun NH2-terminal kinase/stress-activated protein kinase activation by members of the TNF receptor superfamily, including CD27, CD30, CD40, and lymphotoxin-β receptor. To investigate the functional role of TRAF5 in vivo, we generated TRAF5-deficient mice by gene targeting. Activation of either NF-κB or c-Jun NH2-terminal kinase/stress-activated protein kinase by tumor necrosis factor, CD27, and CD40 was not abrogated in traf5(-/-) mice. However, traf5(-/-) B cells showed defects in proliferation and up-regulation of various surface molecules, including CD23, CD54, CD80, CD86, and Fas in response to CD40 stimulation. Moreover, in vitro Ig production of traf5(-/-) B cells stimulated with anti-CD40 plus IL-4 was reduced substantially. CD27-mediated costimulatory signal also was impaired in traf5(-/-) T cells. Collectively, these results demonstrate that TRAF5 is involved in CD40- and CD27-mediated signalling.",

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AU - Matsumoto, M.

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AU - Kobata, T.

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AU - Ware, C. F.

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