Interleukin-13 suppresses interleukin-10 via inhibiting A20 in peripheral B cells of patients with food allergy.
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.
Department of Gastroenterology and Hepatopathy, Chinese PLA General Hospital, Beijing, 100853, China.
Ming-Yang
MY
Li
Department of Medical Oncology, Division of South Building, Chinese PLA General Hospital, Beijing, 100853, China.
Min
M
Zhu
Department of Gastroenterology and Hepatopathy, Chinese PLA General Hospital, Beijing, 100853, China.
En-Qiang
EQ
Linghu
Department of Pharmacy, General Hospital of Shenyang Military Command, Shenyang 110016, PR China.
Fan
F
Feng
Liver Failure Treatment and Research Center, 302nd Military Hospital, Beijing 100039, China.
Bing
B
Zhu
Department of Digestive Endoscopy, Division of South Building, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Cheng
C
Wu
Department of Gastroenterology and Hepatopathy, Chinese PLA General Hospital, Beijing, 100853, China.
Ming-Zhou
MZ
Guo
D000293:Adolescent; D000328:Adult; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005512:Food Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D018793:Interleukin-13 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016269:Milk Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
C508609:IL10 protein, human; D018793:Interleukin-13; D016753:Interleukin-10; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C513261:Tnfaip3 protein, mouse
histone deacetylase; immune regulation; immunity; interleukin-13