IFN-γ-Mediated Inhibition of Human IgE Synthesis by IL-21 Is Associated with a Polymorphism in the<i>IL-21R</i>Gene

Pène, Jérôme; Guglielmi, Laurence; Gauchat, Jean‐François; Harrer, Nathalie; Woisetschläger, Maximilian; Boulay, Véra; Fabre, Jean‐Michel; Demoly, Pascal; Yssel, Hans

doi:10.4049/jimmunol.177.8.5006

Cited by 56 publications

(67 citation statements)

References 35 publications

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“…By the addition of anti-IL-12 or anti-IFN-γ antibody, it was suggested that MN45-induced IL-12 led to IFN-γ induction and that the IFN-γ was involved in the suppression of IgE production without suppressing IL-4 production. It has been reported that IFN-γ not only suppresses IL-4 production by Th2 cells but also regulates IgE class switch recombination in B cells or enhances production of IL-21, which suppresses the synthesis of IgE (Obayashi et al, 2007;Pène et al, 2006;Suto et al, 2002). We suppose that MN45 induces IFN-γ through IL-12 production, 12 production significantly (Fig.…”

Section: Figmentioning

confidence: 69%

Tetragenococcus halophilus MN45 Isolated from Miso Inhibits IgE Production

Ohata¹,

Yoshida²,

Masuda³

et al. 2011

FSTR

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We measured the ability of 100 strains of lactic acid bacteria (LAB) isolated from miso to induce Th1-type cytokines (interleukin (IL)-12 and IFN-γ) using mouse Peyer's patch (PP) cells, and selected Tetragenococcus halophilus MN45 strain (MN45) as the strain with the potential for a strong anti-allergic effect. MN45 cultured in medium containing 15% NaCl for more than 2 days showed the strongest activity of Th1-type cytokine induction among MN45 cultured at various NaCl concentrations and culture times. Next, we analyzed the ability of MN45 to suppress IgE production and the mechanism thereof by neutralizing IL-12 and IFN-γ using PP cells and splenocytes from ovalbumin (OVA)-induced allergic diarrhea model mice. Analysis revealed that MN45 induced IL-12 first, and then IL-12 induced IFN-γ strongly and inhibited IgE production. These results indicate that MN45 may exert an anti-allergic effect.

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Section: Figmentioning

confidence: 69%

Tetragenococcus halophilus MN45 Isolated from Miso Inhibits IgE Production

Ohata¹,

Yoshida²,

Masuda³

et al. 2011

FSTR

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“…Although the role of IL-21 in IgE production from human B cells in vitro has generated conflicting findings (37)(38)(39), IgE is increased in sera of patients with loss-of-function mutations in the IL-21R gene (40). Switching to IgE may initiate within the GC, but IgE + cells can undergo rapid differentiation into plasma cells and are mostly found outside the GC (41).…”

mentioning

confidence: 99%

IL-21 and IL-4 Collaborate To Shape T-Dependent Antibody Responses

McGuire

Vogelzang

Warren

et al. 2015

The Journal of Immunology

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The selection of affinity-matured Ab-producing B cells is supported by interactions with T follicular helper (Tfh) cells. In addition to cell surface–expressed molecules, cytokines produced by Tfh cells, such as IL-21 and IL-4, provide B cell helper signals. In this study, we analyze how the fitness of Th cells can influence Ab responses. To do this, we used a model in which IL-21R–sufficient (wild-type [WT]) and –deficient (Il21r−/−) Ag-specific Tfh cells were used to help immunodeficient Il21r−/− B cells following T-dependent immunization. Il21r−/− B cells that had received help from WT Tfh cells, but not from Il21r−/− Tfh cells, generated affinity-matured Ab upon recall immunization. This effect was dependent on IL-4 produced in the primary response and associated with an increased fraction of memory B cells. Il21r−/− Tfh cells were distinguished from WT Tfh cells by a decreased frequency, reduced conjugate formation with B cells, increased expression of programmed cell death 1, and reduced production of IL-4. IL-21 also influenced responsiveness to IL-4 because expression of both membrane IL-4R and the IL-4–neutralizing soluble (s)IL-4R were reduced in Il21r−/− mice. Furthermore, the concentration of sIL-4R was found to correlate inversely with the amount of IgE in sera, such that the highest IgE levels were observed in Il21r−/− mice with the least sIL-4R. Taken together, these findings underscore the important collaboration between IL-4 and IL-21 in shaping T-dependent Ab responses.

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“…Other reports suggested that IL-21 may indirectly interfere with IgE production through IFN-dependent (21) or -independent (19) mechanisms rather than directly act on B cells. IL-21 may even upregulate IgE production in vitro depending on the culture conditions (20,21).…”

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confidence: 99%

IL-21 Induces Inhibitor of Differentiation 2 and Leads to Complete Abrogation of Anaphylaxis in Mice

Kishida

Hiromura

Shin‐Ya

et al. 2007

The Journal of Immunology

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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.

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IFN-γ-Mediated Inhibition of Human IgE Synthesis by IL-21 Is Associated with a Polymorphism in theIL-21RGene

Cited by 56 publications

References 35 publications

Tetragenococcus halophilus MN45 Isolated from Miso Inhibits IgE Production

Tetragenococcus halophilus MN45 Isolated from Miso Inhibits IgE Production

IL-21 and IL-4 Collaborate To Shape T-Dependent Antibody Responses

IL-21 Induces Inhibitor of Differentiation 2 and Leads to Complete Abrogation of Anaphylaxis in Mice

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