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Background Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, smooth muscle activation and matrix degradation. This study tests the hypothesis that CD4+ T cell-produced IL-17 modulates inflammation and smooth muscle cell activation leading to the pathogenesis of AAA and that human mesenchymal stem cell (MSC) treatment can attenuate IL-17 production and AAA formation. Methods and Results Human aortic tissue demonstrated a significant increase in IL-17 and IL-23 expression in AAA patients compared to controls as analyzed by RT-PCR and ELISA. AAA formation was assessed in C57BL/6 (wild type; WT), IL-23−/− or IL-17−/− mice using an elastase-perfusion model. Heat-inactivated elastase was used as control. On days 3, 7 and 14 following perfusion, abdominal aorta diameter was measured by video micrometry, and aortic tissue was analyzed for cytokines, cell counts and IL-17-producing CD4+ T cells. Aortic diameter and cytokine production (MCP-1, RANTES, KC, TNF-α, MIP-1α and IFN-γ) was significantly attenuated in elastase-perfused IL-17−/− and IL-23−/− mice compared to WT mice on day 14. Cellular infiltration (especially IL-17-producing CD4+ T cells) was significantly attenuated in elastase-perfused IL-17−/− mice compared to WT mice on day 14. Primary aortic smooth muscle cells were significantly activated by elastase or IL-17 treatment. Furthermore, MSC treatment significantly attenuated AAA formation and IL-17 production in elastase-perfused WT mice. Conclusion These results demonstrate that CD4+ T cell-produced IL-17 plays a critical role in promoting inflammation during AAA formation and that immunomodulation of IL-17 by MSCs can offer protection against AAA formation.

Background-Our aim was to establish a novel model of abdominal aortic aneurysms (AAA) in mice using application of peri-adventitial elastase.