Abstract
Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by the production of autoantibodies against the hemidesmosomal protein BP180. B regulatory cells (Bregs) are crucial in maintaining self-tolerance and suppressing autoantibody production. However, it is still unclear whether the dysfunctions of Bregs contributes to the autoantibody production in BP patients. In this study, we found that CD19+CD24hiCD27+ Bregs and IL-10+CD19+ Bregs were significantly increased in the peripheral blood samples of BP patients compared with that in healthy controls. Moreover, compared to Bregs from healthy individuals, we found that Bregs from BP patients fails to suppress the production of specific anti-BP180 autoantibody when co-cultured with patient-derived PBMCs. Additionally, Bregs from BP patients were defective in suppressing the CD4+ T cell proliferation and the cytokines expression (including IFN-γ, TNF-α and IL-4). Notably, we found that patient-derived Bregs produced high level of TNF-α and the TNF inhibitor etanercept could inhibit the autoantibody production in the culture system in vitro. Our results indicate that Bregs from BP patient appear phenotypically pro-inflammatory by their cytokine profile and are defective in immunosuppressive function, which suggest that Bregs play a pro-inflammatory role rather than a regulatory role in the pathogenesis of BP.
Highlights
Bullous pemphigoid (BP) is a prevalent autoimmune blistering disease worldwide, which results from specific antibodies against adhesion molecules BP180 and BP230 of the dermal-epidermal basement membrane zone[1,2]
We found that the frequency of CD19+CD24hiCD27+ B regulatory cells (Bregs) (Fig. 1A and B) and IL-10+CD19+ Bregs (Sup Fig. 2A and B) were both significantly higher in BP patients compared with that in healthy controls (p < 0.05)
Our results indicated that the frequency of CD19+CD24hiCD27+ Bregs in BP patients was elevated compared with that in healthy controls
Summary
Bullous pemphigoid (BP) is a prevalent autoimmune blistering disease worldwide, which results from specific antibodies against adhesion molecules BP180 and BP230 of the dermal-epidermal basement membrane zone[1,2]. Regulatory lymphocytes including regulatory T cells (Tregs) and regulatory B cells (Bregs) play crucial roles in maintaining self-tolerance and preventing autoimmunity disorder. These lymphocytes could regulate antibody production by suppressing the activation of T lymphocytes and the co-stimulatory signaling to activate B cells[5]. Iwata et al confirmed that the CD19+IL-10+ Bregs can be characterized as CD24hiCD27+ B cells in humans peripheral blood[10] These Bregs can suppress the activity of T cells and maintain immune homeostasis mainly via secreting IL-10. Studies showed that in patients with systemic lupus erythematosus (SLE) or diabetes, Bregs showed impairment in immune-suppressive function, leading to the breakdown of self-tolerance[11]. The balance between TNF-α and IL-10 could modulate the effector function of macrophages and cell apoptosis, suggesting an antagonistic effect of TNF-α on immunomodulation of IL-1016
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
