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MALAT1通过促进树突状细胞释放白细胞介素-6和抑制调节性T细胞的免疫调节功能来诱导食物过敏。

MALAT1 Induces Food Allergy by Promoting Release of IL-6 from Dendritic Cells and Suppressing the Immunomodulatory Function of Tregs.

作者信息

Feng Hua, Xiong Xiujuan, Chen Zhuo, Luo Nan, Wu Yongning

机构信息

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330000, People's Republic of China.

School of Public Health, Nanchang University, Nanchang, 330006, People's Republic of China.

出版信息

J Asthma Allergy. 2022 Apr 29;15:529-544. doi: 10.2147/JAA.S341742. eCollection 2022.

DOI:10.2147/JAA.S341742
PMID:35515816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9064454/
Abstract

BACKGROUND

Dendritic cells (DCs) comprise a valuable target for immune-modulation in food allergy (FA). Long noncoding RNA (lncRNA), metastasis associated lung adenocarcinoma transcript 1 (MALAT1) has immunomodulatory capacities and may influence the outcome of DC antigen presentation. However, the precise molecular mechanisms underlying the implication of MALAT1 in FA remain unclear.

METHODS

BALB/c mice were sensitized to ovalbumin in accordance with a model of FA protocol and injected with adenovirus. After modeling, immunohistochemistry was performed to analyze the jejunal tissues of FA mice and hematoxylin-eosin staining and toluidine blue staining were performed to detect inflammation and mast cell numbers. Ovalbumin-sensitized mice were monitored for symptoms of diarrhea and rectal temperature. Immature DCs were stimulated by oxidized low density lipoprotein to trigger their maturation.

RESULTS

MALAT1 was found highly expressed in mice with FA, and its silencing relieved allergic reactions with reduction in intestinal inflammatory cells and mast cells in FA mice. MALAT1 aggravated symptoms by downregulating zinc finger protein 36 (ZFP36). MALAT1 also downregulated ZFP36 expression to promote interleukin-6 (IL-6) secretion by DCs and maturation of DCs, with increased serum-specific immunoglobulin E (IgE) and IgG1 levels.

CONCLUSION

Together, these data suggested that therapeutically blocking MALAT1 in FA could reduce the severity of FA by decreasing secretion of IL-6 by DCs and suppressing the immunomodulation of Tregs.

摘要

背景

树突状细胞（DCs）是食物过敏（FA）免疫调节的重要靶点。长链非编码RNA（lncRNA），即转移相关肺腺癌转录本1（MALAT1）具有免疫调节能力，可能影响DC抗原呈递的结果。然而，MALAT1在FA中的具体分子机制仍不清楚。

方法

按照FA方案模型，用卵清蛋白致敏BALB/c小鼠并注射腺病毒。建模后，进行免疫组化分析FA小鼠的空肠组织，进行苏木精-伊红染色和甲苯胺蓝染色以检测炎症和肥大细胞数量。监测卵清蛋白致敏小鼠的腹泻症状和直肠温度。用氧化型低密度脂蛋白刺激未成熟DCs以触发其成熟。

结果

发现MALAT1在FA小鼠中高表达，其沉默可减轻过敏反应，减少FA小鼠肠道炎症细胞和肥大细胞。MALAT1通过下调锌指蛋白36（ZFP36）加重症状。MALAT1还下调ZFP36表达以促进DCs分泌白细胞介素-6（IL-6）和DCs成熟，血清特异性免疫球蛋白E（IgE）和IgG1水平升高。

结论

总之，这些数据表明，在FA中通过治疗性阻断MALAT1可降低DCs分泌IL-6并抑制调节性T细胞的免疫调节作用，从而减轻FA的严重程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f874/9064454/47f207f3b14d/JAA-15-529-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f874/9064454/368cde4167c4/JAA-15-529-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f874/9064454/47f207f3b14d/JAA-15-529-g0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f874/9064454/1d5a317dc839/JAA-15-529-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f874/9064454/af5d09e4594f/JAA-15-529-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f874/9064454/4fd722d00e38/JAA-15-529-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f874/9064454/368cde4167c4/JAA-15-529-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f874/9064454/47f207f3b14d/JAA-15-529-g0008.jpg

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