Potential Immunopathogenic Role of the Mucosa-Bone Marrow Axis in IgA Nephropathy: Insights From Animal Models

Impaired immune regulation along the mucosa-bone marrow axis has been postulated to play an important role in the pathogenesis of IgA nephropathy. Animal models have allowed us to study such changes in detail. Accumulating evidence from a number of animal models suggest that there is dysregulation of innate and cellular immunity in IgA nephropathy, resulting in changes to the mucosal immune system. These changes appear to be linked closely to a disruption of mucosal tolerance, resulting in the abnormal priming and dissemination of cells to sites such as the bone marrow where they are responsible for the synthesis of nephritogenic IgA. These findings suggest that future treatment strategies should focus on manipulating the priming and dissemination of these memory cells to prevent the appearance of nephritogenic IgA in the systemic compartment.