Junctional adhesion molecule-A on dendritic cells regulates Th1 differentiation

• Published in: Immunology letters 2021-07, Vol.235, p.32-40
• Main Authors: Bonilha, Caio S., Benson, Robert A., Scales, Hannah E., Brewer, James M., Garside, Paul
• Format: Article
• Language: English
• Subjects: Autoimmunity; Biomarkers; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell adhesion; Cell Adhesion - immunology; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Communication; Cell Differentiation - immunology; Coculture Techniques; Cytokines - biosynthesis; Disease Susceptibility; Endothelial Cells - immunology; Endothelial Cells - metabolism; F11R; Humans; Immunological Synapses - metabolism; Immunophenotyping; Inflammation; JAM-A; Lymphocyte Activation - drug effects; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Th1 Cells - cytology; Th1 Cells - immunology; Th1 Cells - metabolism
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/j.imlet.2021.05.001

•JAM-A is present in the immunological synapse during CD4+ T cell priming.•JAM-A plays a role in CD4+ T cell-dendritic cell cluster formation.•JAM-A is required for optimal Th1 differentiation. The junctional adhesion molecule-A (JAM-A) is an adhesion molecule present in the surface of several cell types, such as endothelial cells and leukocytes as well as Dendritic Cells (DC). Given the potential relevance of JAM-A in diverse pathological conditions such as inflammatory diseases and cancer, we investigated the role of JAM-A in CD4+ T cell priming. We demonstrate that JAM-A is present in the immunological synapse formed between T cells and DC during priming. Furthermore, an antagonistic anti-JAM-A mAb could disrupt the interaction between CD4+ T cell and DC. Antagonism of JAM-A also attenuated T cell activation and proliferation with a decrease in T-bet expression and increased IL-6 and IL-17 secretion. These findings demonstrate a functional role for JAM-A in interactions between CD4+ T cells and DCs during T cell priming as a positive regulator of Th1 differentiation.