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Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4–stimulated B cells

2002; Elsevier BV; Volume: 100; Issue: 13 Linguagem: Inglês

10.1182/blood-2002-04-1115

1528-0020

Akira Suto, Hiroshi Nakajima, Koichi Hirose, Kotaro Suzuki, Shin‐ichiro Kagami, Yohei Seto, Aihiro Hoshimoto, Yasushi Saito, Donald C. Foster, Itsuo Iwamoto,

Immunotherapy and Immune Responses

Interleukin 21 (IL-21) has recently been identified as a multifunctional cytokine that induces the proliferation of T cells and B cells and differentiation of natural killer cells. To determine whether IL-21 regulates IL-4–mediated immune responses, we examined the effect of IL-21 on antigen-specific IgE production in mice. We also examined the effect of IL-21 on IL-4–induced IgE production from B cells and antigen-induced T-helper 2 (Th2) cell differentiation. The in vivo injection of IL-21 prevented antigen-specific IgE but not IgG2a production on immunization. IL-21 did not affect Th2 cell differentiation or IL-4 production from CD4+ T cells but directly inhibited IL-4–induced IgE production from B cells at single-cell levels. Moreover, IL-21 inhibited IL-4–induced germ line Cε transcription in B cells without the inhibition of signal transducer and activator of transcription 6 (Stat6) activation. Taken together, these results indicate that IL-21 down-regulates IgE production from IL-4–stimulated B cells through the inhibition of germ line Cε transcription and thus suggest that IL-21 may be useful for the treatment of IgE-dependent allergic diseases.