IL-21-induced Bε cell apoptosis mediated by natural killer T cells suppresses IgE responses

Michishige Harada, Kumiko Magara-Koyanagi, Hiroshi Watarai, Yuko Nagata, Yasuyuki Ishii, Satoshi Kojo, Shigetoshi Horiguchi, Yoshitaka Okamoto, Toshinori Nakayama, Nobutaka Suzuki, Wen Chen Yeh, Shizuo Akira, Hiroshi Kitamura, Osamu Ohara, Ken Ichiro Seino, Masaru Taniguchi

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95 Citations (Scopus)

Abstract

Epidemiological studies have suggested that the recent increase in the incidence and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination; however, the underlying mechanisms remain uncertain. Here, we demonstrate that natural killer T (NKT) cells in mice and humans play a crucial role in the BCG-induced suppression of IgE responses. BCG-activated murine Vα14 NKT cells, but not conventional CD4 T cells, selectively express high levels of interleukin (IL)-21, which preferentially induces apoptosis in Bε cells. Signaling from the IL-21 receptor increases the formation of a complex between Bcl-2 and the proapoptotic molecule Bcl-2-modifying factor, resulting in Bε cell apoptosis. Similarly, BCG vaccination induces IL-21 expression by human peripheral blood mononuclear cells (PBMCs) in a partially NKT cell-dependent fashion. BCG-activated PBMCs significantly reduce IgE production by human B cells. These findings provide new insight into the therapeutic effect of BCG in allergic diseases. JEM

Original languageEnglish
Pages (from-to)2929-2937
Number of pages9
JournalJournal of Experimental Medicine
Volume203
Issue number13
DOIs
Publication statusPublished - Dec 25 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Harada, M., Magara-Koyanagi, K., Watarai, H., Nagata, Y., Ishii, Y., Kojo, S., Horiguchi, S., Okamoto, Y., Nakayama, T., Suzuki, N., Yeh, W. C., Akira, S., Kitamura, H., Ohara, O., Seino, K. I., & Taniguchi, M. (2006). IL-21-induced Bε cell apoptosis mediated by natural killer T cells suppresses IgE responses. Journal of Experimental Medicine, 203(13), 2929-2937. https://doi.org/10.1084/jem.20062206