A link between glomerular IgA nephropathy (IgAN) and T helper 2 (Th2) response has been suggested; however, the mechanisms are poorly defined because of the lack of an appropriate model. Previously, we reported a novel murine model characterized by lineage-restricted deletion of the gene encoding MAD homologue 4 (Smad4) in T cells (Smad4co/co; Lck-cre) and found that Smad4co/co; Lck-cre mice exhibited massive glomerular IgA deposition, increased albumin creatinine ratio, aberrant glycosylated IgA, IgA complexed with IgG1 and IgG2a, and polymeric IgA, all known features of IgAN in humans. These findings indicate that Smad4co/co; Lck-cre mice could be a useful model for studying the mechanisms between IgAN and Th2 response, and furthermore, the disruption of Smad4-dependent signaling in T cells may play an important role in the pathogenesis of human IgAN and contribute to a Th2 T-cell phenotype.
