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

Adv Sci (Weinh). 2023 Mar;10(7):e2206958. doi: 10.1002/advs.202206958. Epub 2023 Jan 2.

Abstract

Development of abdominal aortic aneurysms (AAA) enhances lesion group-2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rorafl/fl Il7rCre/+ mice or induced ILC2 depletion in Icosfl-DTR-fl/+ Cd4Cre/+ 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 Rorafl/fl Il7rCre/+ 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 Ly6Chi monocyte polarization. Reconstitution of WT EOS and ILC2 but not Il5-/- ILC2 slows AAA growth in Rorafl/fl Il7rCre/+ mice by increasing systemic EOS. Besides regulating SMC pathobiology, ILC2 play an indirect role in AAA protection via the IL5 and EOS mechanism.

Keywords: Group-2 innate lymphoid cell; IL5; abdominal aortic aneurysm; eosinophil.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Aneurysm, Abdominal* / immunology
  • Aortic Aneurysm, Abdominal* / pathology
  • Aortic Aneurysm, Abdominal* / prevention & control
  • Eosinophils* / immunology
  • Eosinophils* / pathology
  • Immunity, Innate* / immunology
  • Interleukin-13
  • Interleukin-5* / immunology
  • Lymphocytes* / immunology
  • Mice

Substances

  • Interleukin-13
  • Interleukin-5