JAM-A deficiency alters dendritic cell phenotype in a mouse model of food allergy 2333769

Abstract

Abstract Introduction Food allergy is a growing health concern affecting over 220 million people worldwide. The intestinal epithelial barrier is crucial to food tolerance as its disruption can activate immune cells in the lamina propria and lead to allergic reactions. Junctional Adhesion Molecule A (JAM-A) is a key tight junction protein that maintains barrier integrity. Our previous work showed that JAM-A-/- mice had heightened anaphylaxis compared to wild-type (WT), with males exhibiting stronger Th2 responses than females. Methods Since JAM-A is also expressed on dendritic cells (DCs), we investigated how JAM-A on DCs impacts their differentiation and maturation. Bone marrow DCs from WT and JAM-A-/-mice were cultured with GM-CSF and then stimulated with TLR ligands. Results JAM-A-/- females display elevated IL-12, IL-6 and TNF expression, suggesting a Th1-skewed phenotype. In contrast, JAM-A-/- males exhibit higher MHCII, CD80, and CD86 expression than WT, indicating enhanced antigen-presenting capacity. In addition, naïve JAM-A-/- mice had increased frequencies of live lymph node DCs, indicating a potential role in T-cell priming. Conclusion Overall, our results suggest that BMDCs from male mice are skewed toward a pro-allergic Th2 response. Funding Source NIH Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)