Background/Purpose:

The presentation of chemokines by endothelial cells results in chemoattraction of leukocytes that express the correlative chemokine receptors. In this way, chemokines direct leukocyte trafficking throughout the body. Upon receptor binding, arrested leukocytes, here T cells, firmly adhere to the endothelium and subsequently crawl along the blood vessel wall in search of an area permissive to cellular passage or transmigration. As a result, chemokine induced T cell adhesion is both rapid and polarized. This is in contrast to antigen receptor mediated T cell adhesion, which is characterized by slow kinetics and operates under different physical forces. 

Methods:

Thus, the goal of this work was to identify the unique signaling pathways regulating T cell adhesion downstream of chemokine receptors. 

Results:

We have shown that SDF-1α induced Rap1 activation is transient in comparison to the sustained Rap1 activation observed following stimulation of the T cell receptor. Using an inhibitory RNA screen we have identified that the guanine nucleotide exchange factor mediating SDF-1α-Rap1 activation is PLCε1. Further studies show that knockdown of PLCε1 in T cells interferes with SDF-1α induced Rap1 activation and firm adhesion, as observed through adhesion studies performed under sheer flow. Through the analysis of morphological changes following stimulation, we show that PLCε1 is also necessary for migration. Structure-function analysis of PLCε1 uncovers the contribution of different domains to its guanine exchange activity. 

Conclusion:

In conclusion, we uncover a novel signaling pathway where SDF-1α induces T cell adhesion through activation of PLCε1. While T cell trafficking plays an important role in healthy immune surveillance, inflammatory responses, and autoimmune diseases, chemokine induced signaling cascades are currently understood in only the broadest sense.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/plce1-mediates-cellular-adhesion-downstream-of-sdf-1-in-t-cells/