Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells

The dysfunction of regulatory B cells (Breg) may result in immune inflammation such as allergic rhinitis (AR); the underlying mechanism is not fully understood yet. Short-chain fatty acids, such as propionic acid (PA), have immune regulatory functions. This study is aimed at testing a hypothesis tha...

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Main Authors: Cai-Jie Zhou, Bai-Ling Xie, Hai-Yang Han, Yin Wang, Yong-Hua Wang, Jing-Yi Hong, Yi-Xia Wei, Zhi-Gang Liu, Yan Feng, Gui Yang, Ping-Chang Yang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/2684361
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author Cai-Jie Zhou
Bai-Ling Xie
Hai-Yang Han
Yin Wang
Yong-Hua Wang
Jing-Yi Hong
Yi-Xia Wei
Zhi-Gang Liu
Yan Feng
Gui Yang
Ping-Chang Yang
author_facet Cai-Jie Zhou
Bai-Ling Xie
Hai-Yang Han
Yin Wang
Yong-Hua Wang
Jing-Yi Hong
Yi-Xia Wei
Zhi-Gang Liu
Yan Feng
Gui Yang
Ping-Chang Yang
author_sort Cai-Jie Zhou
collection DOAJ
description The dysfunction of regulatory B cells (Breg) may result in immune inflammation such as allergic rhinitis (AR); the underlying mechanism is not fully understood yet. Short-chain fatty acids, such as propionic acid (PA), have immune regulatory functions. This study is aimed at testing a hypothesis that modulates PA production alleviating airway allergy through maintaining Breg functions. B cells were isolated from the blood obtained from AR patients and healthy control (HC) subjects. The stabilization of IL-10 mRNA in B cells was tested with RT-qPCR. An AR mouse model was developed to test the role of PA in stabilizing the IL-10 expression in B cells. We found that the serum PA levels were negatively correlated with the serum Th2 cytokine levels in AR patients. Serum PA levels were positively associated with peripheral CD5+ B cell frequency in AR patients; the CD5+ B cells were also IL-10+. The spontaneous IL-10 mRNA decay was observed in B cells, which was prevented by the presence of PA through activating GPR43. PA counteracted the effects of Tristetraprolin (TTP) on inducing IL-10 mRNA decay in B cells through the AKT/T-bet/granzyme B pathway. Administration of Yupinfeng San, a Chinese traditional medical formula, or indole-3-PA, induced PA production by intestinal bacteria to stabilize the IL-10 expression in B cells, which promoted the allergen specific immunotherapy, and efficiently alleviated experimental AR. In summary, the data show that CD5+ B cells produce IL-10. The serum lower PA levels are associated with the lower frequency of CD5+ B cells in AR patients. Administration with Yupinfeng San or indole-3-PA can improve Breg functions and alleviate experimental AR.
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issn 2314-7156
language English
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publisher Wiley
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spelling doaj-art-cae56ac116f84668b4af3d862715e38e2025-02-03T07:24:13ZengWileyJournal of Immunology Research2314-71562021-01-01202110.1155/2021/2684361Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B CellsCai-Jie Zhou0Bai-Ling Xie1Hai-Yang Han2Yin Wang3Yong-Hua Wang4Jing-Yi Hong5Yi-Xia Wei6Zhi-Gang Liu7Yan Feng8Gui Yang9Ping-Chang Yang10Shenzhen HospitalGuangdong Provincial Key Laboratory of Regional Immunity and DiseasesGuangdong Provincial Key Laboratory of Regional Immunity and DiseasesShenzhen HospitalShenzhen HospitalGuangdong Provincial Key Laboratory of Regional Immunity and DiseasesShenzhen HospitalGuangdong Provincial Key Laboratory of Regional Immunity and DiseasesDepartment of OtolaryngologyDepartment of OtolaryngologyGuangdong Provincial Key Laboratory of Regional Immunity and DiseasesThe dysfunction of regulatory B cells (Breg) may result in immune inflammation such as allergic rhinitis (AR); the underlying mechanism is not fully understood yet. Short-chain fatty acids, such as propionic acid (PA), have immune regulatory functions. This study is aimed at testing a hypothesis that modulates PA production alleviating airway allergy through maintaining Breg functions. B cells were isolated from the blood obtained from AR patients and healthy control (HC) subjects. The stabilization of IL-10 mRNA in B cells was tested with RT-qPCR. An AR mouse model was developed to test the role of PA in stabilizing the IL-10 expression in B cells. We found that the serum PA levels were negatively correlated with the serum Th2 cytokine levels in AR patients. Serum PA levels were positively associated with peripheral CD5+ B cell frequency in AR patients; the CD5+ B cells were also IL-10+. The spontaneous IL-10 mRNA decay was observed in B cells, which was prevented by the presence of PA through activating GPR43. PA counteracted the effects of Tristetraprolin (TTP) on inducing IL-10 mRNA decay in B cells through the AKT/T-bet/granzyme B pathway. Administration of Yupinfeng San, a Chinese traditional medical formula, or indole-3-PA, induced PA production by intestinal bacteria to stabilize the IL-10 expression in B cells, which promoted the allergen specific immunotherapy, and efficiently alleviated experimental AR. In summary, the data show that CD5+ B cells produce IL-10. The serum lower PA levels are associated with the lower frequency of CD5+ B cells in AR patients. Administration with Yupinfeng San or indole-3-PA can improve Breg functions and alleviate experimental AR.http://dx.doi.org/10.1155/2021/2684361
spellingShingle Cai-Jie Zhou
Bai-Ling Xie
Hai-Yang Han
Yin Wang
Yong-Hua Wang
Jing-Yi Hong
Yi-Xia Wei
Zhi-Gang Liu
Yan Feng
Gui Yang
Ping-Chang Yang
Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells
Journal of Immunology Research
title Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells
title_full Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells
title_fullStr Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells
title_full_unstemmed Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells
title_short Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells
title_sort short chain fatty acids promote immunotherapy by modulating immune regulatory property in b cells
url http://dx.doi.org/10.1155/2021/2684361
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