Epigenetic Regulation via Altered Histone Acetylation Results in Suppression of Mast Cell Function and Mast Cell-Mediated Food Allergic Responses.
Epigenetic Regulation via Altered Histone Acetylation Results in Suppression of Mast Cell Function and Mast Cell-Mediated Food Allergic Responses.
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DOI：
10.3389/fimmu.2018.02414
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发表时间：
2018
影响因子：
7.3
通讯作者：
Mathias CB
中科院分区：
文献类型：
--
作者：
Krajewski D;Kaczenski E;Rovatti J;Polukort S;Thompson C;Dollard C;Ser-Dolansky J;Schneider SS;Kinney SRM;Mathias CB
肥大细胞是高度通用的细胞，其取决于免疫触发物、激活背景和细胞因子刺激而执行多种功能。抗原介导的肥大细胞应答受转录过程调节，该过程导致诱导许多有助于肥大细胞功能的基因。最近，我们还表明，暴露于具有已知表观遗传作用的饮食制剂，如姜黄素，可以抑制肥大细胞介导的食物过敏，这表明体内肥大细胞反应可能是表观遗传调节的。为了进一步评估表观遗传修饰对肥大细胞功能的影响，我们研究了骨髓来源的肥大细胞（BMMC）对组蛋白脱乙酰酶抑制剂-阿司他汀A（TSA）治疗的反应。IgE介导的BMMC激活导致IL-4、IL-6、TNF-α和IL-13的表达和分泌增强。相反，TSA预处理导致细胞因子分泌改变。同时伴有FcεRI表达减少和肥大细胞脱颗粒。有趣的是，暴露于非IgE刺激物如IL-33也受到TSA治疗的影响。此外，持续TSA暴露导致肥大细胞凋亡和存活率下降。进一步的检测显示TSA处理的BMMCs中I-κBα表达增加，磷酸化relA水平降低，提示TSA改变了转录过程，导致I-κBα转录增强，NF-κB活化降低。最后，在卵白蛋白诱导的食物过敏模型中用TSA治疗野生型小鼠导致食物过敏症状的发展显著减弱，包括变应性腹泻和肥大细胞活化的减少。因此，这些数据表明，免疫应答期间肥大细胞活化的表观遗传调节可能通过改变组蛋白乙酰化而发生，并且暴露于膳食物质可能诱导调节肥大细胞功能的表观遗传修饰。
Mast cells are highly versatile cells that perform a variety of functions depending on the immune trigger, context of activation, and cytokine stimulus. Antigen-mediated mast cell responses are regulated by transcriptional processes that result in the induction of numerous genes contributing to mast cell function. Recently, we also showed that exposure to dietary agents with known epigenetic actions such as curcumin can suppress mast cell-mediated food allergy, suggesting that mast cell responses in vivo may be epigenetically regulated. To further assess the effects of epigenetic modifications on mast cell function, we examined the behavior of bone marrow-derived mast cells (BMMCs) in response to trichostatin A (TSA) treatment, a well-studied histone deacetylase inhibitor. IgE-mediated BMMC activation resulted in enhanced expression and secretion of IL-4, IL-6, TNF-α, and IL-13. In contrast, pretreatment with TSA resulted in altered cytokine secretion. This was accompanied by decreased expression of FcεRI and mast cell degranulation. Interestingly, exposure to non-IgE stimuli such as IL-33, was also affected by TSA treatment. Furthermore, continuous TSA exposure contributed to mast cell apoptosis and a decrease in survival. Further examination revealed an increase in I-κBα and a decrease in phospho-relA levels in TSA-treated BMMCs, suggesting that TSA alters transcriptional processes, resulting in enhancement of I-κBα transcription and decreased NF-κB activation. Lastly, treatment of wild-type mice with TSA in a model of ovalbumin-induced food allergy resulted in a significant attenuation in the development of food allergy symptoms including decreases in allergic diarrhea and mast cell activation. These data therefore suggest that the epigenetic regulation of mast cell activation during immune responses may occur via altered histone acetylation, and that exposure to dietary substances may induce epigenetic modifications that modulate mast cell function.
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DOI：
10.4049/jimmunol.1303026
发表时间：
2014-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Johnston LK;Chien KB;Bryce PJ
通讯作者：
Bryce PJ
影响因子：
--
作者：
Huber, Lars C.;Distler, Joerg H. W.;Juengel, Astrid
通讯作者：
Juengel, Astrid
DOI：
10.2165/00066982-200307030-00008
发表时间：
2003-01-01
期刊：
Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology
影响因子：
--
作者：
Bottero, Virginie;Imbert, Veronique;Peyron, Jean-Francois
通讯作者：
Peyron, Jean-Francois
影响因子：
2.6
作者：
Dunlop, Joan H.;Keet, Corinne A.
通讯作者：
Keet, Corinne A.
DOI：
10.1073/pnas.90.6.2532
发表时间：
1993-03-15
影响因子：
11.1
作者：
BROWN, K;PARK, S;SIEBENLIST, U
通讯作者：
SIEBENLIST, U