Mesenteric IL-10-producing CD5+ regulatory B cells suppress cow's milk casein-induced allergic responses in mice.

A-Ram Kim,Bokyung Kim,Michael A Beaven,Young Hwan Park,Young Mi Kim,Jun Ho Lee,Wahn Soo Choi,Hyung Sik Kim,Seung Taek Nam,Hyuk Soon Kim,Hyun Woo Kim,Do Kyun Kim,Min Bum Lee,Dajeong Lee

doi:10.1038/srep19685

Abstract

Food allergy is a hypersensitive immune reaction to food proteins. We have previously demonstrated the presence of IL-10-producing CD5+ B cells and suggested their potential role in regulating cow’s milk casein allergy in humans and IgE-mediated anaphylaxis in mice. In this study, we determined whether IL-10-producing CD5+ regulatory B cells control casein-induced food allergic responses in mice and, if so, the underlying mechanisms. The induction of oral tolerance (OT) by casein suppressed casein-induced allergic responses including the decrease of body temperature, symptom score, diarrhea, recruitment of mast cells and eosinophils into jejunum, and other biological parameters in mice. Notably, the population of IL-10-producing CD5+ B cells was increased in mesenteric lymph node (MLN), but not in spleen or peritoneal cavity (PeC) in OT mice. The adoptive transfer of CD5+ B cells from MLN, but not those from spleen and PeC, suppressed the casein-induced allergic responses in an allergen-specific and IL-10-dependent manner. The inhibitory effect of IL-10-producing CD5+ B cells on casein-induced allergic response was dependent on Foxp3+ regulatory T cells. Taken together, mesenteric IL-10-producing regulatory B cells control food allergy via Foxp3+ regulatory T cells and could potentially act as a therapeutic regulator for food allergy.

Highlights

The prevalence of food allergy, an adverse immune reaction to allergenic food proteins[1,2], is increasing and affects approximately 6–8% of children in the United States of America
We report that mesenteric lymph node (MLN)-derived IL-10-producing CD5+ B cells can suppress casein-induced allergy in a mouse model
Regulatory T (Treg) cells are reported to participate in the induction of oral tolerance (OT) in a murine model[6,29,30], but whether regulatory B (Breg) cells play an additional complementary role is unknown

Summary

Introduction

The prevalence of food allergy, an adverse immune reaction to allergenic food proteins[1,2], is increasing and affects approximately 6–8% of children in the United States of America. Further studies indicate that a specific B subsets including CD5+, CD1dhiCD5+, and T2-MZP inhibit immune responses through the production of IL-10, and named regulatory B (Breg) cells or B10 cells[22,23]. These cells are reported to suppress mouse autoimmunity and allergic inflammation in disease models that include contact hypersensitivity (CHS), experimental autoimmune encephalomyelitis (EAE) and systemic lupus erythematosus (SLE)[18,24,25]. We previously described the potential inhibitory role of IL-10-producing CD5+ B cells in human food allergic patients[26,27] and in IgE-mediated allergic responses[28]. It is still unclear whether or not IL-10-producing CD5+ B cells suppress food allergic responses and, if so, by what mechanism

Methods

Results

Conclusion