Abstract
The regulatory B cells (Breg) are important in the body immunity. The differentiation process of Breg is not fully understood yet. Ubiquitin A20 has immune regulatory functions. This study aims to investigate the role of A20 in the regulation of interleukin (IL)-10 in B cells. In this study, B cells were isolated from the peripheral blood samples of healthy subjects and patients with food allergy (FA). The B cells were analyzed by flow cytometry, real time RT-PCR, Western blotting and chromatin immunoprecipitation. We observed that the frequency of Breg and the levels of A20 in B cells were markedly lower in FA patients than in healthy controls. In vitro deletion of A20 compromised the expression of IL-10. B cells in FA patients showed higher levels of histone deacetylase (HDAC)-11 than in healthy subjects. Exposure to IL-13 in the culture induced high levels of HDAC11 in B cells. IL-13 also repressed the expression of A20 in B cells, in which HDAC11 played a critical role via inducing the chromatin remoldeling at the IL-10 promoter locus. Mice with A20-deficient B cells are prone to FA. In summary, ubiquitin A20 can increase the IL-10 expression in B cells, which can be affected by the IL-13-induced HDAC11. To inhibit HDAC11 may have therapeutic potential for FA.
Highlights
B cells (BC) are a major fraction of the immune cells in the body
The results showed that the frequency of IL-10+ Bregs was significantly less in food allergy (FA) patients than in healthy subjects
It is accepted that the immune tolerance plays a critical role in the maintenance of homeostasis in the intestine [21]; the breakdown of immune tolerance plays a role in the initiation of food allergy [22]
Summary
B cells (BC) are a major fraction of the immune cells in the body. Apart from producing antibodies, B cells have an immune regulatory function via producing immune regulatory cytokines, such as interleukin (IL)-10 [1] or transforming growth factor (TGF)-β [2, 3]. It is reported that the IL-10+ BCs had immune regulatory function and the frequency of IL-10+ BC was less in several immune disorders, including allergic diseases [5, 6], which can be restored by specific allergen immunotherapy [7]. Food allergy (FA) is an abnormal immune response that is induced by the immune cells in the intestine over reacting to the innocent food allergens [8]. Re-exposure to specific antigens triggers the sensitized mast cells to release allergic mediators to induce allergic response [8]. Immune response is tightly regulated by the immune system, mainly regulated by regulatory T cells or/and regulatory B cells [9].
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