Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line C(epsilon) transcription of IL-4-stimulated B cells.
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 (T(h)2) cell differentiation. The in vivo injection of IL-21 prevented antigen-specific IgE but not IgG2a production on immunization. IL-21 did not affect T(h)2 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 C(epsilon) 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 C(epsilon) transcription and thus suggest that IL-21 may be useful for the treatment of IgE-dependent allergic diseases.
Suto
Akira
A
Department of Internal Medicine II, Chiba University School of Medicine, Chiba City, Japan.
Nakajima
Hiroshi
H
Hirose
Koichi
K
Suzuki
Kotaro
K
Kagami
Shin-ichiro
S
Seto
Yohei
Y
Hoshimoto
Aihiro
A
Saito
Yasushi
Y
Foster
Donald C
DC
Iwamoto
Itsuo
I
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003864:Depression, Chemical; D005803:Genes, Immunoglobulin; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000187:drug effects*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000378:metabolism / Q000502:physiology*; D007378:Interleukins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000098546:Interleukin-21
D000941:Antigens; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007378:Interleukins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D000098546:Interleukin-21