Figure 1. Schematic representation of VSMC signaling mechanisms involved in T cell recruitment following acute arterial injury.

During vascular injury and deendothelialization, VSMC migration and activation recruits immune cells such as macrophages and T cells, resulting in the formation of a neointimal lesion. In their study in this issue of the JCI, Kovacic et al. show that TNF-α activation of TNF-α–R1 on VSMCs results in the stimulation of NF-κB (p65 subunit) and STAT3 pathways (9). The complexes formed by NF-κB, STAT3, and p21^Cip1 are found in the activated, neointimal VSMCs. Combinatorial action of NF-κB and STAT3 turns on the transcription of the RANTES gene, which encodes the T cell chemokine RANTES (also known as CCL5). Secreted RANTES acts on its receptor, CCR5, on T cells to induce chemotaxis, thus allowing T cell entry into the neointimal lesion. TRADD, TNFRSF1A-associated via death domain.