Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy
Sustaining higher frequency of mast cells in the allergic lesion site has been recognized. Factors causing high numbers of mast cells in the local tissues are not fully understood yet. RAS signaling plays a role in sustaining certain cell activities. This study is aimed at elucidating the role of RA...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/5414993 |
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| author | Huang Huang Yu Liu Yanan Wang Huazhen Liu Bailing Xie Michael B. W. Zheng Liteng Yang Qinmiao Huang Yongjin Wu Gaohui Wu Pengyuan Zheng Pingchang Yang |
| author_facet | Huang Huang Yu Liu Yanan Wang Huazhen Liu Bailing Xie Michael B. W. Zheng Liteng Yang Qinmiao Huang Yongjin Wu Gaohui Wu Pengyuan Zheng Pingchang Yang |
| author_sort | Huang Huang |
| collection | DOAJ |
| description | Sustaining higher frequency of mast cells in the allergic lesion site has been recognized. Factors causing high numbers of mast cells in the local tissues are not fully understood yet. RAS signaling plays a role in sustaining certain cell activities. This study is aimed at elucidating the role of RAS activation in the apoptosis resistance induction in mast cells and at employing semaphorin 3A to regulate RAS activities in sensitized mast cells and alleviating the allergic response in the intestine. A food allergy (FA) mouse model was developed. Mast cells were isolated from FA mouse intestinal tissues by flow cytometry. Mast cell apoptosis was assessed by staining with annexin V and propidium iodide. We found that aberrantly higher p21-activated kinase-1 (Pak1) expression in FA mast cells was associated with mast cell aggregation in the intestine. Sensitization increased Pak1 expression and apoptosis resistance in intestinal mast cells. RAS and Pak1 mutually potentiated each other in sensitized mast cells. Semaphorin 3A (sema3A) suppressed the Pak1 expression and RAS activation in mast cells. sema3A restored the apoptosis sensitivity in sensitized mast cells. Administration of sema3A potentiated allergen-specific immunotherapy in experimental FA. In conclusion, mast cells of FA mice showed higher Pak1 expression and high RAS activation status that contributed to apoptosis resistance in mast cells. Administration of sema3A restored the sensitivity to apoptosis inducers and promoted the therapeutic effects of specific immunotherapy on experimental FA. |
| format | Article |
| id | doaj-art-14e1d9d30dae48e8b9f08be1daa3b3b7 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-14e1d9d30dae48e8b9f08be1daa3b3b72025-08-20T03:54:29ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/5414993Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food AllergyHuang Huang0Yu Liu1Yanan Wang2Huazhen Liu3Bailing Xie4Michael B. W. Zheng5Liteng Yang6Qinmiao Huang7Yongjin Wu8Gaohui Wu9Pengyuan Zheng10Pingchang Yang11Department of GastroenterologyDepartment of General PracticeDepartment of GastroenterologyGuangdong Provincial Key Laboratory of Regional Immunity and DiseasesGuangdong Provincial Key Laboratory of Regional Immunity and DiseasesDepartment of Life ScienceDepartment of RespirologyDepartment of RespirologyLonggang ENT Hospital & Shenzhen ENT InstituteDepartment of RespirologyDepartment of GastroenterologyGuangdong Provincial Key Laboratory of Regional Immunity and DiseasesSustaining higher frequency of mast cells in the allergic lesion site has been recognized. Factors causing high numbers of mast cells in the local tissues are not fully understood yet. RAS signaling plays a role in sustaining certain cell activities. This study is aimed at elucidating the role of RAS activation in the apoptosis resistance induction in mast cells and at employing semaphorin 3A to regulate RAS activities in sensitized mast cells and alleviating the allergic response in the intestine. A food allergy (FA) mouse model was developed. Mast cells were isolated from FA mouse intestinal tissues by flow cytometry. Mast cell apoptosis was assessed by staining with annexin V and propidium iodide. We found that aberrantly higher p21-activated kinase-1 (Pak1) expression in FA mast cells was associated with mast cell aggregation in the intestine. Sensitization increased Pak1 expression and apoptosis resistance in intestinal mast cells. RAS and Pak1 mutually potentiated each other in sensitized mast cells. Semaphorin 3A (sema3A) suppressed the Pak1 expression and RAS activation in mast cells. sema3A restored the apoptosis sensitivity in sensitized mast cells. Administration of sema3A potentiated allergen-specific immunotherapy in experimental FA. In conclusion, mast cells of FA mice showed higher Pak1 expression and high RAS activation status that contributed to apoptosis resistance in mast cells. Administration of sema3A restored the sensitivity to apoptosis inducers and promoted the therapeutic effects of specific immunotherapy on experimental FA.http://dx.doi.org/10.1155/2022/5414993 |
| spellingShingle | Huang Huang Yu Liu Yanan Wang Huazhen Liu Bailing Xie Michael B. W. Zheng Liteng Yang Qinmiao Huang Yongjin Wu Gaohui Wu Pengyuan Zheng Pingchang Yang Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy Journal of Immunology Research |
| title | Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy |
| title_full | Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy |
| title_fullStr | Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy |
| title_full_unstemmed | Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy |
| title_short | Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy |
| title_sort | semaphorin 3 promotes specific immunotherapy effects on experimental food allergy |
| url | http://dx.doi.org/10.1155/2022/5414993 |
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