DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows’ milk allergy in mouse model
Background Cows’ milk allergy (CMA) is a hypersensitivity immune reaction brought on by specific immunologic mechanisms to cow’s milk proteins. As one of the most common food allergies in infants, the incidence of CMA during the first year of life is estimated to be nearly 7.5%. Due to the limitatio...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-12-01
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| Series: | Autoimmunity |
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| Online Access: | http://dx.doi.org/10.1080/08916934.2020.1836490 |
| _version_ | 1797684737083441152 |
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| author | Beibei Sun Dongjin Feng Guangmeng Wang Xiaohong Yu Zhongmao Dong Ling Gao |
| author_facet | Beibei Sun Dongjin Feng Guangmeng Wang Xiaohong Yu Zhongmao Dong Ling Gao |
| author_sort | Beibei Sun |
| collection | DOAJ |
| description | Background Cows’ milk allergy (CMA) is a hypersensitivity immune reaction brought on by specific immunologic mechanisms to cow’s milk proteins. As one of the most common food allergies in infants, the incidence of CMA during the first year of life is estimated to be nearly 7.5%. Due to the limitation in the knowledge of the pathological mechanism underlying CMA, however, the clinical interventions and therapies remain very unsatisfactory. Aim of the study The transcriptional factor FOXP3 possesses crucial roles in CMA, and increased FOXP3 mRNA expression has a predictive function in faster acquisition of tolerance in infants with CMA. But the exact mechanism remains not fully elucidated. Methods For PAG treatment, PAG (dissolved in saline 30 mg/mL, 0, 5, 10, 20 mg/kg BW) was administered daily intraperitoneally (ip) for one week at the time that 6 weeks after the CMP sensitisation. Results In the present study, we revealed that the expression of FOXP3 is significantly up-regulated in PBMCs from CMA patients and CMA mice on mRNA and protein level. Furthermore, a dramatic reduction in the FOXP3 TSDR methylation and a significant increase in the expression of TET2 are observed in CMA patients and CMA mice. More importantly, we found that propargylglycine (PAG) significantly alleviates symptoms of CMA in mice by suppressing the expression of FOXP3 through restoring TET2 expression. Conclusions Our work revealed a novel function of PAG on CMA, which may provide a deeper insight into the pathomechanism of CMA and a novel therapy target for CMA clinical interventions. |
| first_indexed | 2024-03-12T00:34:07Z |
| format | Article |
| id | doaj.art-65200b298f394ec8a26fde8a4498dfed |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:34:07Z |
| publishDate | 2020-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-65200b298f394ec8a26fde8a4498dfed2023-09-15T10:01:09ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2020-12-0153846747510.1080/08916934.2020.18364901836490DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows’ milk allergy in mouse modelBeibei Sun0Dongjin Feng1Guangmeng Wang2Xiaohong Yu3Zhongmao Dong4Ling Gao5Department of Gastroenterology, Xuzhou Children’s Hospital, Xuzhou Medical UniversityDepartment of Gastroenterology, Xuzhou Children’s Hospital, Xuzhou Medical UniversityDepartment of Gastroenterology, Xuzhou Children’s Hospital, Xuzhou Medical UniversityDepartment of Gastroenterology, Xuzhou Children’s Hospital, Xuzhou Medical UniversityDepartment of Gastroenterology, Xuzhou Children’s Hospital, Xuzhou Medical UniversityDepartment of Gastroenterology, Xuzhou Children’s Hospital, Xuzhou Medical UniversityBackground Cows’ milk allergy (CMA) is a hypersensitivity immune reaction brought on by specific immunologic mechanisms to cow’s milk proteins. As one of the most common food allergies in infants, the incidence of CMA during the first year of life is estimated to be nearly 7.5%. Due to the limitation in the knowledge of the pathological mechanism underlying CMA, however, the clinical interventions and therapies remain very unsatisfactory. Aim of the study The transcriptional factor FOXP3 possesses crucial roles in CMA, and increased FOXP3 mRNA expression has a predictive function in faster acquisition of tolerance in infants with CMA. But the exact mechanism remains not fully elucidated. Methods For PAG treatment, PAG (dissolved in saline 30 mg/mL, 0, 5, 10, 20 mg/kg BW) was administered daily intraperitoneally (ip) for one week at the time that 6 weeks after the CMP sensitisation. Results In the present study, we revealed that the expression of FOXP3 is significantly up-regulated in PBMCs from CMA patients and CMA mice on mRNA and protein level. Furthermore, a dramatic reduction in the FOXP3 TSDR methylation and a significant increase in the expression of TET2 are observed in CMA patients and CMA mice. More importantly, we found that propargylglycine (PAG) significantly alleviates symptoms of CMA in mice by suppressing the expression of FOXP3 through restoring TET2 expression. Conclusions Our work revealed a novel function of PAG on CMA, which may provide a deeper insight into the pathomechanism of CMA and a novel therapy target for CMA clinical interventions.http://dx.doi.org/10.1080/08916934.2020.1836490cows’ milk allergy (cma)foxp3tsdr methylationtet2dl-propargylglycine |
| spellingShingle | Beibei Sun Dongjin Feng Guangmeng Wang Xiaohong Yu Zhongmao Dong Ling Gao DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows’ milk allergy in mouse model Autoimmunity cows’ milk allergy (cma) foxp3 tsdr methylation tet2 dl-propargylglycine |
| title | DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows’ milk allergy in mouse model |
| title_full | DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows’ milk allergy in mouse model |
| title_fullStr | DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows’ milk allergy in mouse model |
| title_full_unstemmed | DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows’ milk allergy in mouse model |
| title_short | DL-propargylglycine administration inhibits TET2 and FOXP3 expression and alleviates symptoms of neonatal Cows’ milk allergy in mouse model |
| title_sort | dl propargylglycine administration inhibits tet2 and foxp3 expression and alleviates symptoms of neonatal cows milk allergy in mouse model |
| topic | cows’ milk allergy (cma) foxp3 tsdr methylation tet2 dl-propargylglycine |
| url | http://dx.doi.org/10.1080/08916934.2020.1836490 |
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