AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation.

The mechanisms driving T cell homing to lymph nodes and migration to tissue are well described but little is known about factors that affect T cell egress from tissues. Here, we generate mice with a T cell-specific deletion of the scaffold protein A kinase anchoring protein 9 (AKAP9) and use models of inflammatory disease to demonstrate that AKAP9 is dispensable for T cell priming and migration into tissues and lymph nodes, but is required for T cell retention in tissues. AKAP9 deficiency results in increased T cell egress to draining lymph nodes, which is associated with impaired T cell re-activation in tissues and protection from organ damage. AKAP9-deficient T cells exhibit reduced microtubule-dependent recycling of TCRs back to the cell surface and this affects antigen-dependent activation, primarily by non-classical antigen-presenting cells. Thus, AKAP9-dependent TCR trafficking drives efficient T cell re-activation and extends their retention at sites of inflammation with implications for disease pathogenesis.

Citation

Jan M Herter, Nir Grabie, Xavier Cullere, Veronica Azcutia, Florencia Rosetti, Paul Bennett, Grit S Herter-Sprie, Wassim Elyaman, Francis W Luscinskas, Andrew H Lichtman, Tanya N Mayadas. AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation. Nature communications. 2015;6:10182

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PMID: 26680259

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