Pak1 Kinase Promotes Activated T Cell Trafficking by Regulating the Expression of L-Selectin and CCR7

• Published in: Frontiers in immunology 2019, Vol.10, p.370-370
• Main Authors: Dios-Esponera, Ana, Melis, Nicolas, Subramanian, Bhagawat C, Weigert, Roberto, Samelson, Lawrence E
• Format: Article
• Language: English
• Subjects: CCR7; Immunology; L-selectin; L-selectin shedding; lymph node trafficking; Pak1 kinase
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.00370

Normal function of the adaptive immune system requires trafficking of T cells between the blood and lymphoid organs. Lymphocyte homing to lymph nodes requires that they cross endothelial barriers present in blood vessels and lymphatics. This multi-step process requires a remodeling of the lymphocyte plasma membrane, which is mediated by the dynamic re-arrangement of the actin cytoskeleton. Pak1 plays a central role in cell morphology, adhesion and migration in various cell types. Here we demonstrate that Pak1 is required for activated CD4 T cell trafficking to lymph nodes. Pak1 deficiency in T cells causes a defect in the transcription of CCR7 and L-selectin, thereby altering lymphocyte trafficking. Additionally, we report an increase in L-selectin shedding in Pak1-deficient T cells, which correlates with a decrease in the recruitment of calmodulin to the cytoplasmic tail of L-selectin during T cell activation. Overall, our findings demonstrate that by regulating the expression of two major lymph node homing molecules, L-selectin and CCR7, Pak1 mediates activated CD4 T cell trafficking.