Journal of Asthma and Allergy (Apr 2022)
MALAT1 Induces Food Allergy by Promoting Release of IL-6 from Dendritic Cells and Suppressing the Immunomodulatory Function of Tregs
Abstract
Hua Feng,1,2 Xiujuan Xiong,3 Zhuo Chen,1 Nan Luo,2 Yongning Wu1,4,5 1State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330000, People’s Republic of China; 2School of Public Health, Nanchang University, Nanchang, 330006, People’s Republic of China; 3Department of Pathology, Basic Medical College of Nanchang University, Nanchang, 330006, People’s Republic of China; 4China National Center for Food Safety Risk Assessment, Beijing, 100022, People’s Republic of China; 5Chinese Academy of Medical Science Research Unit, Beijing, 100730, People’s Republic of ChinaCorrespondence: Yongning Wu, State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330000, People’s Republic of China, Tel +86-10-52165589, Email [email protected]: 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.Keywords: food allergy, metastasis associated in lung adenocarcinoma transcript 1, zinc finger protein 36, dendritic cells, interleukin 6, Tregs, immunomodulation
