Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

Development of abdominal aortic aneurysms (AAA) enhances lesion group-2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rora(fl/fl)Il7r(Cre/+) mice or induced ILC2 depletion in Icos(fl-DTR-fl/+)Cd4(Cre/+) mice expedites AAA growth, increases lesion inflammation, but leads to systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies show that ILC2 protect mice from AAA formation via IL5 and EOS. IL5 or ILC2 from wild-type (WT) mice, but not ILC2 from Il5(-/-) mice induces EOS differentiation in bone-marrow cells from Rora(fl/fl)Il7r(Cre/+) mice. IL5, IL13, and EOS or ILC2 from WT mice, but not ILC2 from Il5(-/-) and Il13(-/-) mice block SMC apoptosis and promote SMC proliferation. EOS but not ILC2 from WT or Il5(-/-) mice block endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6C(hi) monocyte polarization. Reconstitution of WT EOS and ILC2 but not Il5(-/-) ILC2 slows AAA growth in Rora(fl/fl)Il7r(Cre/+) mice by increasing systemic EOS. Besides regulating SMC pathobiology, ILC2 play an indirect role in AAA protection via the IL5 and EOS mechanism.

Automated summary

The development of abdominal aortic aneurysms (AAA) leads to an increase in the accumulation of lesion group-2 innate lymphoid cells (ILC2) and IL5 in the blood. Deficiency of ILC2 or induced depletion of ILC2 in mice results in accelerated AAA growth, increased lesion inflammation, and systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies reveal that ILC2 protect against AAA formation through the IL5 and EOS pathways. IL5 or ILC2 from wild-type (WT) mice induces EOS differentiation in bone marrow cells from ILC2-deficient mice, while IL5, IL13, and EOS or ILC2 from WT mice promote smooth muscle cell (SMC) proliferation and prevent SMC apoptosis. EOS from WT or IL5-deficient mice inhibits endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6C(hi) monocyte polarization. Reconstitution of WT EOS and ILC2 slows AAA growth in mice by increasing systemic EOS, while ILC2 indirectly contributes to AAA protection through the IL5 and EOS mechanism.