IL-21 induces inhibitor of differentiation 2 and leads to complete abrogation of anaphylaxis in mice.
IL-21 exerts pleiotrophic immunomodulatory activities on a variety of target cells including B cells that undergo class switch recombination (CSR) to IgE. In this study, we examined whether IgE-mediated systemic anaphylaxis was controlled by in vivo administration of IL-21 using the peanut allergy model in mice and investigated the molecular mechanisms underlying the IL-21-induced regulation of IgE. The anaphylactic reaction was completely abolished by the administration of recombinant mouse IL-21 or an IL-21 expression plasmid in terms of the change of body temperature and anaphylactic symptoms. The recombinant mouse IL-21 treatment remarkably suppressed IgE CSR in splenic B cells, resulting in significant decrease in serum concentrations of total as well as allergen-specific IgE. In the meanwhile, IL-21 provoked B cells in normal as well as allergic mice to express the inhibitor of differentiation 2 (Id2) gene that was shown to be crucially involved in the regulation of the activation-induced cytidine deaminase and IgE CSR. Moreover, mice genetically deficient for Id2 were completely unsusceptible to IL-21-induced prevention of IgE CSR and anaphylaxis. The present study strongly suggests that IL-21 is capable of regulating systemic allergic reactions by inducing the transcriptional regulator Id2, and the cytokine may be useful for clinical intervention for allergic diseases including anaphylaxis.
Department of Microbiology, Kyoto Prefectural University of Medicine, Japan.
Tsunao
T
Kishida
Yayoi
Y
Hiromura
Masaharu
M
Shin-Ya
Hidetsugu
H
Asada
Hiroko
H
Kuriyama
Manabu
M
Sugai
Akira
A
Shimizu
Yoshifumi
Y
Yokota
Takemitsu
T
Hama
Jiro
J
Imanishi
Yasuo
Y
Hisa
Osam
O
Mazda
D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000276:immunology; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D021183:Peanut Hypersensitivity / Q000276:immunology*; D000098546:Interleukin-21
D051797:Inhibitor of Differentiation Protein 2; D007378:Interleukins; D007073:Immunoglobulin E; D000098546:Interleukin-21