B cell–derived IL-4 acts on podocytes to induce proteinuria and foot process effacement

• DOI: 10.1172/jci.insight.81836
• Publication Date: 2017-11-01T15:00:36Z
• Authors: Alfred H.J. Kim; Jun-Jae Chung; Shreeram Akilesh; Ania Koziell; Sanjay Jain; Jeffrey B. Hodgin; Mark J. Miller; Thaddeus S. Stapp...; Jeffrey H. Miner; Andrey S. Shaw
• Keywords: Minimal change disease

The efficacy of B cell depletion therapies in diseases such as nephrotic syndrome and rheumatoid arthritis suggests a broader role cells human disease than previously recognized. In some these diseases, the minimal change subtype syndrome, pathogenic antibodies immune complexes are not involved. We hypothesized that cells, activated kidney, might produce cytokines capable directly inducing injury proteinuria. To test our hypothesis, we targeted model antigen to kidney glomerulus showed transfer antigen-specific could induce glomerular This effect was mediated by IL-4, IL-4–deficient did Overexpression IL-4 mice sufficient proteinuria be attenuated JAK kinase inhibitors. Since is specific activator STAT6, analyzed biopsies demonstrated STAT6 activation up 1 3 patients, suggesting or IL-13 exposure patients. These data suggest cytokines.