Interleukin-13 suppresses interleukin-10 via inhibiting A20 in peripheral B cells of patients with food allergy

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.

Modulation of allergic inflammation in the lung by a peptide derived from Mycobacteria tuberculosis chaperonin 60.1

“…The role of A20 in inflammatory conditions has been well documented. An important anti‐inflammatory role for this ubiquitin has been reported in arthritis, auto‐immune diseases, cardiovascular diseases, cystic fibrosis, chronic obstructive pulmonary disease (COPD), allergies and asthma . In addition, the modulation of the expression of A20 has been demonstrated to be an important mechanism of action of certain drugs including methotrexate, quercetin and the combination of long‐acting β 2 ‐adrenoceptor agonistsand glucocorticoids .…”

“…An important anti-inflammatory role for this ubiquitin has been reported in arthritis, auto-immune diseases, cardiovascular diseases, cystic fibrosis, chronic obstructive pulmonary disease (COPD), allergies and asthma. 20,[27][28][29][30][31][32][33] In addition, the modulation of the expression of A20 has been demonstrated to be an important mechanism of action of certain drugs including methotrexate, quercetin and the combination of long-acting β 2 -adrenoceptor agonistsand glucocorticoids. [34][35][36][37] Moreover, it has recently been reported that there is a positive association between a polymorphism in the A20 gene and susceptibility to human asthma in the population investigated in the GABRIELA study, a study that focuses on the effects of farm environments on asthma and allergy in children from central Europe.…”

A20 enhances the radiosensitivity of hepatocellular carcinoma cells to 60Co-γ ionizing radiation

“…RNA was reverse-transcribed into cDNA by a Multiscribe™ Reverse Transcriptase kit (Applied Biosystems, Foster City, CA, USA). Real time PCR (qPCR) was performed following the primers and protocol provided by Li et al [ 31 ].…”

HDAC11 regulates type I interferon signaling through defatty-acylation of SHMT2

“…There are 18HDACs in mammals that are classified into four classes. Class III HDACs (known as sirtuins) are NAD + -dependent, while class I, II and IV HDACs are all zinc-dependent.Class I HDACs, which consists of HDAC1, 2, 3, and 8, are homologous to yeast Rpd3.Class II HDACs are homologous to yeast Hda1 and can be further divided into two subclasses: IIa (HDAC4,5,7,9) and IIb (HDAC6, 10) 1,3 . Class IV HDAC, which is not highly homologous to either Rpd3 or Hda1 yeast enzymes, is comprised solely of HDAC11 4,5 .HDAC11 is normally found in brain, testis, and immune cells such as antigenpresenting cells (APCs) 5,6 .…”

“…Class II HDACs are homologous to yeast Hda1 and can be further divided into two subclasses: IIa (HDAC4,5,7,9) and IIb (HDAC6, 10) 1,3 . Class IV HDAC, which is not highly homologous to either Rpd3 or Hda1 yeast enzymes, is comprised solely of HDAC11 4,5 .…”