The mucosa-bone-marrow axis in IgA nephropathy.
Large numbers of studies have demonstrated that abnormal humoral and cellular immunity may contribute to the pathogenesis of IgA nephropathy. On the other hand, clinical evidence indicates that bone marrow cells and mucosal immunity may also play a key role. Based on these findings, impaired immune regulation in the 'mucosa-bone-marrow axis' has been postulated in IgA nephropathy patients. However, the underlying mechanisms still remain unclear. This is mainly due to difficulties in the clinical approach to the complicated immune system. Therefore, appropriate animal models are required. We recently established several useful animal models. Using these models, our group is approaching underlying mechanisms in which bone marrow and mucosal cells interrelate and finally induce this disease. Up to now, results from these models and its clinical feedback have suggested that mucosal IgA responses to antigens may be altered by Th2-biased background or dysregulation of innate immunity in this disease. This abnormal mucosal IgA immune system may result in failure of mucosal antigen elimination and thus increases in memory cells in the bone marrow.
Suzuki
Yusuke
Y
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan. yusuke@med.juntendo.ac.jp
Tomino
Yasuhiko
Y
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D009092:Mucous Membrane / Q000276:immunology*