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

被引：63

作者：

Kim, Alfred H. J. ^{[1
]}

Chung, Jun-Jae ^{[2
]}

Akilesh, Shreeram ^{[2
]}

Koziell, Ania ^{[3
,4
]}

Jain, Sanjay ^{[5
]}

Hodgin, Jeffrey B. ^{[6
]}

Miller, Mark J. ^{[2
]}

Stappenbeck, Thaddeus S. ^{[2
]}

Miner, Jeffrey H. ^{[5
]}

Shaw, Andrey S. ^{[2
,7
]}

机构：

[1] Washington Univ, Sch Med, Dept Internal Med, Div Rheumatol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Pathol & Immunol, Div Immunobiol, St Louis, MO 63110 USA

[3] Kings Coll London, Dept Expt Immunobiol, Div Transplantat Immunol & Mucosal Biol, London, England

[4] Evelina Childrens Hosp, Dept Paediat Nephrol, London, England

[5] Washington Univ, Sch Med, Renal Div, St Louis, MO USA

[6] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[7] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA

来源：

JCI INSIGHT | 2017年 / 2卷 / 21期

关键词：

FOCAL SEGMENTAL GLOMERULOSCLEROSIS; VERSUS-HOST-DISEASE; INTERLEUKIN-4 TRANSGENIC MICE; CHILDHOOD NEPHROTIC-SYNDROME; MESSENGER-RNA EXPRESSION; PLACEBO-CONTROLLED TRIAL; IGA NEPHROPATHY; IN-VIVO; CRESCENTIC GLOMERULONEPHRITIS; MONOCLONAL-ANTIBODY;

D O I：

10.1172/jci.insight.81836

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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

引用

页数：17