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

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

doi:10.1182/blood-2002-04-1115

Cited by 209 publications

(206 citation statements)

References 43 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: 98%

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: 98%

Tetragenococcus halophilus MN45 Isolated from Miso Inhibits IgE Production

Ohata¹,

Yoshida²,

Masuda³

et al. 2011

FSTR

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“…Total cellular RNA was prepared, and RT-PCR analysis was performed as previously described (24). In brief, Flag-IL-25R-expressing WT MEF or TRAF6 Ϫ/Ϫ MEF were stimulated with anti-Flag mAb (2 g/ml) at 37°C for 3 h and the total cellular RNA was isolated using Isogen solution (Nippon Gene) according to the manufacturer's instruction.…”

Section: Rt-pcrmentioning

confidence: 99%

Involvement of TNF Receptor-Associated Factor 6 in IL-25 Receptor Signaling

Maezawa

Nakajima

Suzuki

et al. 2006

The Journal of Immunology

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IL-25 (IL-17E) induces IL-4, IL-5, and IL-13 production from an unidentified non-T/non-B cell population and subsequently induces Th2-type immune responses such as IgE production and eosinophilic airway inflammation. IL-25R is a single transmembrane protein with homology to IL-17R, but the IL-25R signaling pathways have not been fully understood. In this study, we investigated the signaling pathway under IL-25R, especially the possible involvement of TNFR-associated factor (TRAF)6 in this pathway. We found that IL-25R cross-linking induced NF-κB activation as well as ERK, JNK, and p38 activation. We also found that IL-25R-mediated NF-κB activation was inhibited by the expression of dominant negative TRAF6 but not of dominant negative TRAF2. Furthermore, IL-25R-mediated NF-κB activation, but not MAPK activation, was diminished in TRAF6-deficient murine embryonic fibroblast. In addition, coimmunoprecipitation assay revealed that TRAF6, but not TRAF2, associated with IL-25R even in the absence of ligand binding. Finally, we found that IL-25R-mediated gene expression of IL-6, TGF-β, G-CSF, and thymus and activation-regulated chemokine was diminished in TRAF6-deficient murine embryonic fibroblast. Taken together, these results indicate that TRAF6 plays a critical role in IL-25R-mediated NF-κB activation and gene expression.

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“…Whether IL-21 regulates IL-4-induced Th2 cell differentiation directly (32,33) or amplifies Th2-driven responses by downregulating the expansion of IFN-g-producing Th1 cells (33,34) remains incompletely understood. Under Th2 polarizing conditions in vitro a significant number of IL-21 + cells coexpress IL-4 (35), and a deficiency in the IL-21R is associated with decreases in both serum IL-4 and IL-4R expression on macrophages following infection (31) and in allergic responses (36).…”

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

Cited by 209 publications

References 43 publications

Tetragenococcus halophilus MN45 Isolated from Miso Inhibits IgE Production

Tetragenococcus halophilus MN45 Isolated from Miso Inhibits IgE Production

Involvement of TNF Receptor-Associated Factor 6 in IL-25 Receptor Signaling

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

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