Theranostics 2019; 9(10):2800-2811. doi:10.7150/thno.34414

Research Paper

Vasoactive intestinal peptide stabilizes intestinal immune homeostasis through maintaining interleukin-10 expression in regulatory B cells

Xiong Sun1, Chuanyong Guo1, Fang Zhao2, Jianhuan Zhu1, Yilu Xu1, Zhi-Qiang Liu4, Gui Yang4, Yuan-Yi Zhang4, Xia Gu4, Liang Xiao5, Zhanju Liu3✉, Ping-Chang Yang4✉

1. Department of Gastroenterology, Shanghai PuTuo District People's Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China.
2. Department of Geriatric Medicine, Shanghai PuTuo District People's Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China.
3. Department of Gastroenterology, The Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
4. Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
5. BGI Shenzhen, Shenzhen, China.

Abstract

Rationale: Immune dysfunction is thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). However, the underlying mechanism requires further investigation. Vasoactive intestinal peptide (VIP) has immune regulatory functions, but its role in immune regulatory activities in the intestinal mucosa is not fully understood. This study aims to elucidate the role of VIP in the regulation of regulatory B cell (Breg) function in the intestine.

Methods: Peripheral blood samples were collected from UC patients and healthy control (HC) subjects. Bregs were isolated from these samples and their immune regulatory function was analyzed. A murine colitis model was established to test the role of VIP in inhibiting inflammation in the intestine.

Results: Serum IL-10 and VIP levels were lower in IgE+ (≥0.35 IU/mL) UC patients than that in HC subjects. The immune suppressive function of Bregs isolated from IgE+ UC patients was impaired. IL-10 mRNA decayed spontaneously in Bregs, which was reversed by VIP added to the culture. Tristetraprolin (TTP) bound IL-10 mRNA to speed its decay, which was blocked by VIP in the culture. Administration of VIP efficiently inhibited experimental colitis.

Conclusions: Insufficient VIP levels in the microenvironment speeds IL-10 mRNA decay to cause Breg dysfunction. Administration of VIP can inhibit experimental colitis, suggesting the translational potential of VIP in the treatment of IgE+ UC.

Keywords: colitis, intestine, interleukin-10, vasoactive intestinal peptide, food allergy

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How to cite this article:
Sun X, Guo C, Zhao F, Zhu J, Xu Y, Liu ZQ, Yang G, Zhang YY, Gu X, Xiao L, Liu Z, Yang PC. Vasoactive intestinal peptide stabilizes intestinal immune homeostasis through maintaining interleukin-10 expression in regulatory B cells. Theranostics 2019; 9(10):2800-2811. doi:10.7150/thno.34414. Available from http://www.thno.org/v09p2800.htm