Related Experiment Video
Updated: Sep 6, 2025
Antigenic Liposomes for Generation of Disease-specific Antibodies
Published on: October 25, 2018
Semaphorin-3 Promotes Specific Immunotherapy Effects on Experimental Food Allergy
Huang Huang1, Yu Liu2, Yanan Wang1
1Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Abstract:
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.
Insights
Mast cells resist apoptosis in food allergies due to elevated RAS signaling and Pak1. Semaphorin 3A (sema3A) reversed this, enhancing immunotherapy effectiveness in a mouse model.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Mast cells accumulate at allergic lesion sites, but the mechanisms driving their high numbers are unclear.
- RAS signaling pathways are implicated in maintaining cellular functions, potentially influencing mast cell survival.
- Understanding mast cell apoptosis resistance is crucial for developing effective allergy treatments.
Purpose of the Study:
- To investigate the role of RAS activation in inducing apoptosis resistance in mast cells.
- To explore the potential of semaphorin 3A (sema3A) in regulating RAS activity and alleviating allergic responses.
- To examine the impact of sema3A on mast cell apoptosis and its synergy with immunotherapy in a food allergy model.
Main Methods:
- Developed a food allergy (FA) mouse model.
- Isolated mast cells from FA mouse intestinal tissues using flow cytometry.
- Assessed mast cell apoptosis via annexin V and propidium iodide staining.
- Evaluated the effects of semaphorin 3A (sema3A) on RAS activation, Pak1 expression, and mast cell apoptosis sensitivity.
Main Results:
- FA mast cells exhibited higher p21-activated kinase-1 (Pak1) expression, linked to intestinal mast cell aggregation.
- Mast cell sensitization increased Pak1 expression and promoted apoptosis resistance.
- RAS and Pak1 mutually amplified each other in sensitized mast cells.
- Semaphorin 3A (sema3A) suppressed Pak1 and RAS activation, restoring apoptosis sensitivity in sensitized mast cells.
- Sema3A administration enhanced allergen-specific immunotherapy efficacy in experimental FA.
Conclusions:
- Elevated Pak1 expression and RAS activation in FA mouse mast cells contribute to apoptosis resistance.
- Semaphorin 3A (sema3A) effectively restores apoptosis sensitivity in mast cells.
- Sema3A shows promise in improving the therapeutic outcomes of specific immunotherapy for food allergies.
