Functional gap junctions accumulate at the immunological synapse and contribute to T cell activation

Mendoza-Naranjo, Ariadna; Bouma, Gerben; Pereda, Cristián; Ramiŕez, Marcos; Webb, Kevin F.; Tittarelli, Andrés; Loṕez, Mercedes N.; Kalergis, Alexis M.; Thrasher, Adrian J.; Becker, David L.; Salazar-Onfray, Flavio

Abstract

Gap junction (GJ) mediates intercellular communication through linked hemichannels from each of two adjacent cells. Using human and mouse models, we show that connexin 43 (Cx43), the main GJ protein in the immune system, was recruited to the immunological synapse during T cell priming as both GJs and stand-alone hemichannels. Cx43 accumulation at the synapse was Ag specific and time dependent, and required an intact actin cytoskeleton. Fluorescence recovery after photobleaching and Cx43- specific inhibitors were used to prove that intercellular communication between T cells and dendritic cells is bidirectional and specifically mediated by Cx43. Moreover, this intercellular cross talk contributed to T cell activation as silencing of Cx43 with an antisense or inhibition of GJ docking impaired intracellular Ca2+ responses and cytokine release by T cells. These findings identify Cx43 as an important functional component of the immunological synapse and reveal a crucial role for GJs and hemichannels as coordinators of the dendritic cell-T cell signaling machinery that regulates T cell activation. Copyright © 2011 by The American Association of Immunologists, Inc.

Citation

Mendoza-Naranjo, A., Bouma, G., Pereda, C., Ramiŕez, M., Webb, K. F., Tittarelli, A., Loṕez, M. N., Kalergis, A. M., Thrasher, A. J., Becker, D. L., & Salazar-Onfray, F. (2011). Functional gap junctions accumulate at the immunological synapse and contribute to T cell activation. Journal of Immunology, 187(6), 3121-3132. https://doi.org/10.4049/jimmunol.1100378

• Journal Article Type: Article
• Acceptance Date: Jul 14, 2011
• Publication Date: Sep 15, 2011
• Deposit Date: Apr 20, 2024
• Publicly Available Date: Jul 10, 2024
• Journal: Journal of Immunology
• Print ISSN: 0022-1767
• Electronic ISSN: 1550-6606
• Publisher: American Association of Immunologists
• Peer Reviewed: Peer Reviewed
• Volume: 187
• Issue: 6
• Pages: 3121-3132
• DOI: https://doi.org/10.4049/jimmunol.1100378
• Public URL: https://nottingham-repository.worktribe.com/output/4831747
• Publisher URL: https://journals.aai.org/jimmunol/article/187/6/3121/85771/Functional-Gap-Junctions-Accumulate-at-the