Mucosal Immune Responses in &lt;i&gt;W/W&lt;sup&gt;v&lt;/sup&gt;&lt;/i&gt; and Sl/Sld Mutant Mice

Yoshino, Naoto; Kanno, Hiroyuki; Takahashi, Kiyomi; Endo, Masahiro; Sato, Shigehiro

doi:10.1538/expanim.61.407

Cited by 6 publications

(6 citation statements)

References 61 publications

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“…Mast cell deficiency has been associated with reduced intestinal IgA responses though the mechanism involved has been unclear ( 23 , 41 ). Prior studies relied on mice with c-Kit deficiency ( 41 ) or mast cell depletion by Diptheria toxin (DT) treatment in transgenic hosts (RMB mice) ( 23 ) to test the role of mast cells.…”

Section: Discussionmentioning

confidence: 99%

Mast cells help organize the Peyer’s patch niche for induction of IgA responses

De Giovanni,

Vykunta,

Biram

et al. 2024

Sci. Immunol.

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Peyer’s patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses that give rise to many intestinal IgA-secreting cells. Induction of isotype switching to IgA in PPs requires interactions between B cells and TGFβ-activating conventional dendritic cells type 2 (cDC2s) in the subepithelial dome (SED). However, the mechanisms promoting cDC2 positioning in the SED are unclear. Here, we found that PP cDC2s express GPR35, a receptor that promotes cell migration in response to various metabolites, including 5-hydroxyindoleacetic acid (5-HIAA). In mice lacking GPR35, fewer cDC2s were found in the SED, and frequencies of IgA + germinal center (GC) B cells were reduced. IgA plasma cells were reduced in both the PPs and lamina propria. These phenotypes were also observed in chimeric mice that lacked GPR35 selectively in cDCs. GPR35 deficiency led to reduced coating of commensal bacteria with IgA and reduced IgA responses to cholera toxin. Mast cells were present in the SED, and mast cell–deficient mice had reduced PP cDC2s and IgA + cells. Ablation of tryptophan hydroxylase 1 (Tph1) in mast cells to prevent their production of 5-HIAA similarly led to reduced PP cDC2s and IgA responses. Thus, mast cell–guided positioning of GPR35 + cDC2s in the PP SED supports induction of intestinal IgA responses.

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Section: Discussionmentioning

confidence: 99%

Mast cells help organize the Peyer’s patch niche for induction of IgA responses

De Giovanni,

Vykunta,

Biram

et al. 2024

Sci. Immunol.

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“…Furthermore, we used three distinct immunization regimens (Figure 3A). All mice were immunized three times at weekly intervals, so the schedule was largely similar to that used in previous studies …”

Section: Methodsmentioning

confidence: 99%

“…All mice were immunized three times at weekly intervals, so the schedule was largely similar to that used in previous studies. 14,[25][26][27][28]…”

Section: Immunization Of Micementioning

confidence: 99%

Critical micelle concentration and particle size determine adjuvanticity of cyclic lipopeptides

et al. 2018

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Cyclic lipopeptides such as surfactin and polymyxin have potent mucosal adjuvant properties. Cyclic lipopeptides are tensioactive compounds but the relationship between adjuvanticity and surface activity is unknown. Here, we show that the critical micelle concentration (cmc) of surfactant and particle size of the surfactant-protein complex are important determinants of cyclic lipopeptide adjuvanticity. We found that the diameter of cyclic lipopeptide-ovalbumin (OVA) complex particles was significantly larger than that in the solutions of OVA alone at cyclic lipopeptide concentrations above the cmc. OVA-specific antibody titers in mice immunized intranasally with OVA and a cyclic lipopeptide at concentrations above its cmc were significantly higher than those in mice immunized with OVA plus the same dose of the cyclic lipopeptide but administered with formulations in which cyclic lipopeptide concentration was below the cmc. Thus, the concentration of the cyclic lipopeptide in the formulation at immunization, but not its overall dose, was critical for its adjuvanticity. Furthermore, two types of aggregates, the cyclic lipopeptide simplex micelles and the cyclic lipopeptide-OVA complex micelles, were found in formulations with SF concentrations above its cmc. Degranulation of mast cells exposed to SF simplex micelles was more pronounced when SF concentration was above the cmc. In conclusion, our study showed that surface activity properties, such as the cmc and the size of surfactant-protein complex contribute to the adjuvanticity of cyclic lipopeptides. Our study proposes a novel idea that cmc is a key parameter for tensioactive adjuvants. This article is protected by copyright. All rights reserved.

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“…Mice, lightly anesthetized with ketamine, were intranasally immunized with 5‐μL aliquots (2.5 μL/nostril) of normal saline containing 100 μg of OVA with or without 500 μg of SF. All groups of mice were immunized three times at weekly intervals, according to the schedule that was largely the same as that used in previous studies .…”

Section: Methodsmentioning

confidence: 99%

Mast cells partially contribute to mucosal adjuvanticity of surfactin in mice

Yoshino

Takeshita

Kawamura

et al. 2017

Immunity Inflam & Disease

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IntroductionSurfactin (SF) is a cyclic lipopeptide that has potent mucosal adjuvant properties. However, immunological mechanisms of SF adjuvant action have not yet been elucidated. As some cyclic lipopeptides, such as polymyxin, can stimulate histamine release from mast cells, we hypothesized that mast cell activation is critical for SF adjuvanticity.Methods/ResultsWe observed that following intranasal immunization with ovalbumin (OVA) plus SF, the titers of the OVA‐specific antibody (Ab) in the mucosal secretions and plasma of mast cell‐deficient mice were significantly lower than those in congenic normal mice, although OVA‐specific Ab did not entirely disappear from mast cell‐deficient mice. SF induced degranulation of mast cells and release of histamine in vitro. To investigate whether SF stimulated mast cells in vivo, we measured body temperature of mice immunized intranasally with OVA plus SF because histamine level affects body temperature. Following immunizations, body temperature of immunized congenic normal mice transiently decreased, whereas body temperature of mast cell‐deficient mice did not change. Plasma levels of OVA‐specific IgE Ab were not significantly different in mast cell‐deficient and congenic normal mice. These findings suggest that SF directly affected mast cells in an IgE Ab‐independent fashion. Furthermore, we analyzed the effects of SF on MC/9 mast cells cultured in vitro. MC/9 cells stimulated by SF released not only histamine but also leukotriene B4 and prostaglandin D2. Moreover, SF up‐regulated mRNA expression levels of Tnf, Ccr5, and Il4 genes in mast cells. These cytokines may play a facilitating role in OVA‐specific immune responses in mice.ConclusionOverall, our results showed that mast cell activation partially mediated SF adjuvanticity.

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Mucosal Immune Responses in <i>W/W<sup>v</sup></i> and Sl/Sld Mutant Mice

Cited by 6 publications

References 61 publications

Mast cells help organize the Peyer’s patch niche for induction of IgA responses

Mast cells help organize the Peyer’s patch niche for induction of IgA responses

Critical micelle concentration and particle size determine adjuvanticity of cyclic lipopeptides

Mast cells partially contribute to mucosal adjuvanticity of surfactin in mice

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