Retinoic Acid Regulates Allergic Inflammation via Limiting Mast Cell Activation

Food Sci Nutr. 2025 Jan 7;13(1):e4727. doi: 10.1002/fsn3.4727. eCollection 2025 Jan.

Abstract

BackgroundAllergic diseases have become one of the major public health problems to be addressed in the world today. As a tissue resident cell, mast cells are crucial in the pathogenesis of allergic diseases. Vitamin A is an important fat-soluble vitamin with immunomodulatory functions. Vitamin A deficiency has been shown to be associated with allergic disease states, including asthma; however, no studies have been reported on whether vitamin A deficiency has an effect on the activation of mast cells in allergic reactions. ObjectiveTo explore whether blocking retinoic acid receptors has an effect on mast cell degranulation. Methods Flow cytometry was used to analyze the expression of FCεRIα and CD117 on the cell surface, toluidine blue staining was used to visualize cellular features and morphological changes. ELISA was used to detect histamine release. High-throughput transcriptome sequencing and qRT-PCR were used to detect the expression of relevant signaling pathways and cytokine genes. Western blot was used to detect the expression of relevant signaling pathway proteins. ResultsIn the present study, we found that antagonism of the retinoic acid receptor (RAR) resulted in overactive mast cells and increased their degranulation. Furthermore, inflammatory signaling pathways such as MyD88-IKK-NF-κB and PI3K-Akt-m-TOR were involved in the effect of retinoic acid (RA) on the activation state of mast cells. ConclusionsIn this paper, we demonstrated that blocking RAR can exacerbate its activation state in IgE-mediated mast cells. This study provided new insights into the possibility that vitamin A deficiency exacerbated mast cell activation and thus affectd allergic diseases and their mechanisms.

Keywords: RAR; allergic diseases; mast cell; retinoic acid receptor; vitamin A.