Abstract
Allergen-specific immunotherapy (SIT) is the mainstay in the treatment of allergic diseases; its therapeutic efficacy is to be improved. Bacterial flagellin (FGN) has immune regulatory functions. This study investigates the role of FGN in promoting immunotherapy efficacy through modulating oxidative stress in regulatory B cells (Bregs). Blood samples were collected from patients with food allergy (FA) and healthy control (HC) subjects. CD19+ CD5+ Bregs were purified from blood samples by flow cytometry cell sorting. A murine FA model was developed with ovalbumin as the specific antigen. The results showed that peripheral Bregs from FA patients showed lower TLR5-related signals and higher apoptotic activities. The peripheral Breg frequency was negatively correlated with serum FGN levels in FA patients. Exposure to a specific antigen in culture induced antigen-specific Breg apoptosis that was counteracted by the presence of FGN. FGN diminished specific antigen-induced oxidative stress in Bregs. The STAT3/MAPKp38/NF-κB signal pathway was involved in the FGN/TLR5 signal-promoted superoxide dismutase expression in Bregs. Administration of FGN promotes the SIT efficacy in suppressing experimental FA. In summary, administration of FGN promotes SIT efficacy on FA, suggesting that the combination of FGN and SIT can be a novel therapy that has the translational potential to be employed in the treatment of allergic diseases.
Highlights
Allergen-specific immunotherapy (SIT) is the mainstay in the treatment of allergic diseases currently
Prompted by previous studies that show CD5+ B cells express IL-10 and have immune regulatory properties [19, 20], blood samples were collected from 30 food allergy (FA) patients and 30 healthy control (HC) subjects
Upon exposure to a specific antigen (OVA), Reactive oxygen species (ROS) levels were markedly increased in specific Bregs (sBregs), and the superoxide dismutase (SOD) levels were markedly decreased in sBregs, but not in naïve Regulatory B cells Tregs (Bregs)
Summary
Allergen-specific immunotherapy (SIT) is the mainstay in the treatment of allergic diseases currently. By administration of small doses of specific allergens, regulatory immune cells, such as regulatory T cells (Tregs) and regulatory B cells (Bregs), are generated to suppress the aberrant immune responses and to alleviate or to cure allergic diseases [1,2,3]. By producing interleukin- (IL-) 10 or/and transforming growth factor- (TGF-) beta, Bregs suppress other immune cells’ activities that plays a critical role in maintaining the immune homeostasis in the body [6]. It is reported that the Breg amounts are fewer or Bregs are dysfunctional in subjects with allergic disorders [6, 7]. The underlying mechanism of maintaining Bregs at functional status is not fully understood yet; factors causing Breg dysfunction are to be further elucidated
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