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Regulatory B cells contribute to allergen-encapsulating nanoparticle immunotherapy efficacy for food allergy
Laila M. Rad, Michael N. Saunders, Laura A. Williams, Katarzyna W. Janczak, Chris Dorsett, Kate V. Griffin, Elizabeth J. Bealer, Jeffrey A. Ma, Sayre A. Tillery, Jyotirmoy Roy, Stephen D. Miller, Jessica J. O’Konek, Lonnie D. Shea
Laila M. Rad, Michael N. Saunders, Laura A. Williams, Katarzyna W. Janczak, Chris Dorsett, Kate V. Griffin, Elizabeth J. Bealer, Jeffrey A. Ma, Sayre A. Tillery, Jyotirmoy Roy, Stephen D. Miller, Jessica J. O’Konek, Lonnie D. Shea
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Research Article Cell biology Immunology

Regulatory B cells contribute to allergen-encapsulating nanoparticle immunotherapy efficacy for food allergy

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Abstract

B cells contribute to the pathogenesis of food allergies as they induce allergen-specific antibody production. Clinically used allergen-specific immunotherapies have been shown to induce regulatory B cell subsets as well as target and reduce allergy-driving B cell functions. This report aims to elucidate the contribution of regulatory B cells to an allergen-encapsulating nanoparticle (aeNP) immunotherapy in a murine model of food allergy. In this model, B cells directly associated with aeNPs. CD20+ B cell depletion after aeNP treatment increased the number of mice with severe allergic reactions during oral food challenges and reduced the expansion of regulatory immune cells including CD103+ DCs and CCR9+ gut-homing Tregs, indicating that B cells are a component of aeNP immunomodulation. B cell communication in the gastrointestinal tract of aeNP-treated mice identified CD23 signaling as a potential inducer of regulatory CD103+ DC functions and disrupter of allergy-driving B cell–T cell communication. These tolerogenic signaling patterns were also identified in IL-10+ B cells, which are known to impart regulatory immune effects in both murine and human disease. Ultimately, B cells are a component of the complex immunomodulation leading to aeNP efficacy at reducing allergic reactivity.

Authors

Laila M. Rad, Michael N. Saunders, Laura A. Williams, Katarzyna W. Janczak, Chris Dorsett, Kate V. Griffin, Elizabeth J. Bealer, Jeffrey A. Ma, Sayre A. Tillery, Jyotirmoy Roy, Stephen D. Miller, Jessica J. O’Konek, Lonnie D. Shea

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Figure 3

Regulatory cell types induced by aeNP treatment are affected by B cell depletion.

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Regulatory cell types induced by aeNP treatment are affected by B cell d...
One day after OFC 7, spleens and SILP were harvested for flow cytometry to characterize splenic DCs (A) and SILP T cells (B). (A) Splenic CD103+ DC counts in OVA NP–treated mice and allergic controls (PBS) with and without B cell depletion. (B) The proportion of Tregs expressing the gut-homing marker CCR9 of all CD4+ T cells in the SILP in OVA NP–treated mice and allergic controls (PBS) with and without B cell depletion. Data shown as mean ± SD; statistically significant differences were identified using 2-way ANOVA with a post hoc Šidák’s test; adjusted P values are shown above significance brackets and sample size at the bottom of each bar (n = 4–9). *P < 0.05, **P < 0.01, ***P < 0.001, NS = not significant.

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