Deficiency of γδT cells protects against abdominal aortic aneurysms by regulating phosphoinositide 3-kinase/AKT signaling.

Abstract

It is known that T lymphocytes are activated in human abdominal aortic aneurysms (AAAs). γδT cells, as a subset of T cells, play a role in many inflammation-related diseases. However, whether γδT cells participate in the formation of AAA remains unknown. In this study, we explored the role of γδT cells in AAA lesions. Using the porcine pancreatic elastase-induced AAA model, we found that knock out of γδT cells significantly attenuated AAA formation. To elucidate how γδT cells contribute to AAA, microarray analysis was performed, which found that the phosphoinositide 3-kinase/AKT signaling pathway was activated in elastase-perfused γδT knockout (γδT KO) mice. By studying differentially expressed genes involved in phosphoinositide 3-kinase signaling, we found that proliferation-related genes (Sos1, Mtor, Myc) were upregulated whereas apoptosis-related genes (Pten, Bcl1, Bad) were downregulated in elastase-perfused γδT KO mice. Furthermore, histopathologic analysis showed increased PCNA⁺ and decreased TUNEL⁺ cells in elastase-perfused γδT KO mice compared with wild-type mice. In addition, inflammatory cytokines including interleukin-1β, Mcp-1, and tumor necrosis factor-α were downregulated in the aneurysm tissues of elastase-perfused γδT KO mice. These data reveal a pathogenic role of γδT cells in the experimental AAA model, likely through mechanisms regulating cell proliferation and mediating inflammatory response. Thus, targeting of γδT cells may offer a potential therapeutic method for aortic aneurysms.