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.
Kishida
Tsunao
T
Department of Microbiology, Kyoto Prefectural University of Medicine, Japan.
Hiromura
Yayoi
Y
Shin-Ya
Masaharu
M
Asada
Hidetsugu
H
Kuriyama
Hiroko
H
Sugai
Manabu
M
Shimizu
Akira
A
Yokota
Yoshifumi
Y
Hama
Takemitsu
T
Imanishi
Jiro
J
Hisa
Yasuo
Y
Mazda
Osam
O
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