The role of the Jak‐Stat pathway in chemokine‐mediated signaling in T lymphocytes

Abstract

Chemokines are low molecular weight soluble mediators that control leukocyte trafficking during lymphocyte homeostasis and inflammation. Chemokine-mediated signaling is triggered upon chemokine binding to seven transmembrane G protein-coupled receptors. Multiple signaling pathways are activated leading to cytoskeleton rearrangements, gene transcription and receptor internalization or degradation Among the signaling molecules involved in chemokine mediated signaling, the Jak-Stat pathway has been shown to be activated very early after chemokine stimulation. There is growing evidence showing the involvement of particular Jaks and Stats, in chemokine receptor signaling both in cell lines and primary cells. Jak/Stat phosphorylation is detected soon after chemokine receptor dimerization or in response to chemokines. Also, pharmacological inhibition of Jaks, or the use of Jak deficient lymphocytes results in inhibition of chemokine-mediated responses, such as chemotaxis or integrin-mediated adhesion. This review summarizes the current data describing the involvement of the Jak-Stat pathway in chemokine-mediated signaling in T lymphocytes and discusses the potential crosstalk with other TCR and cytokine-mediated signaling pathways.