IDENTIFYING THE MECHANISMS OF LYMPH NODE HYPERTROPHY IN ATHEROSCLEROTIC MICE

Abstract

ApoE mice develop hypertrophic lymph nodes and these lymph nodes may contribute to impaired immunity in the mice.

Our results demonstrated that hypertrophic lymph nodes displayed a significant increase over WT mice in lymph node cellularity, T and B cells but no differences were observed in the ratio of CD4 to CD8 T cells, T cell activation and general organization of the lymph node microenvironment.

These hypertrophic lymph nodes were mediated by impaired lymphocyte egress from the organ and impaired egress is induced by the lymph node microenvironment. These include reduced S1P levels, altered S1P concentration gradient, increased CCL21 retention signal, disrupted fluid flow and vessel dysfunction in efferent and lymph node lymphatic vessels.

Finally, treating apoE-/- mice with the cholesterol lowering drug Ezetimibe ameliorated lymph node hypertrophy and leads to a partial restoration of cellular egress through changes in the lymph node microenvironment.