Control of Dendritic Cell Maturation and Migration by the RhoGTPase Regulators SWAP-70 and DEF6.

• Applicant: Dr. Carlos Ocaña Morgner, Ph.D.
• Subject Area: Immunology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259606265

Dendritic cell (DC) maturation and their subsequent migration to lymphoid tissues are key mechanisms to initiate adaptive immune responses and to induce immune tolerance. We have recently published new mechanisms of control of DC function by the protein SWAP-70, e.g. up-regulation of MHCII molecules, S1P-mediated migration and endocytosis, and spontaneous maturation. SWAP-70 regulates these DC functions through interaction and regulation of RhoGTPases, particularly RhoA activation. Preliminary data show that besides SWAP-70, the only closely related protein DEF6 also controls spontaneous maturation and migration of DCs. In an antangonistic manner, both proteins also control surface expression of the adhesion molecule nectin-3, which has not yet been described for DCs. This proposal aims at understanding the combined role of SWAP-70 and DEF6 in DCs to develop a more coherent model of control mechanisms. Discovering new elements regulating these functions and their mechanisms of action is of vital importance to understand DC biology.

• DFG Programme: Research Grants