Critical role of Kupffer cell CD89 expression in experimental IgA nephropathy

In this study,
we generated a CD89 transgenic mouse strain using an authentic murine CD14
promotor with
CD89 expression on blood and tissue monocytes/macrophages. These animals, however,
showed no signs of IgAN but displayed concomitant increased clearance of mouse
serum IgA.In
these experiments Kupffer cells were the predominant cell type in the
degradation of experimentally-induced human IgA, especially human IgA1 catabolized
by these cells. Injecting large quantities of purified IgA from IgAN patients
into CD89 Tg mice triggers IgAN, and concomitant dysfunctional endocytosis and
elimination of patient IgA, resulting in the deposition of CD89-IgA in kidneys
of Tg mice. Our results indicate that although CD89 plays an important role
in IgA and IgA-IC clearance, defective endocytosis of underglycosylated IgA is necessary
for the
development of experimental IgAN.