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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Oncotarget 2015 ; 6 (24): 20037-42 Nephropedia Template TP
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A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation #MMPMID26343524
Wienke J; Janssen W; Scholman R; Spits H; van Gijn M; Boes M; van Montfrans J; Moes N; de Roock S
Oncotarget 2015[Aug]; 6 (24): 20037-42 PMID26343524show ga
Mutations in STAT3 have recently been shown to cause autoimmune diseases through increased lymphoproliferation. We describe a novel Pro471Arg STAT3 mutation in a patient with multiple autoimmune diseases, causing hyperactivation of the Th17 pathway. We show that IL-17 production by primary T cells was enhanced and could not be further increased by IL-6, while IL-10 reduced Th17 cell numbers. Moreover, specific inhibition of STAT3 activation resulted in diminished IL-17 production. We show that the Pro471Arg STAT3 mutation yields both increased levels of IgA and IgG, probably due to high IL-21 levels. When remission was reached through medical intervention, IL-17 levels normalized and the clinical symptoms improved, supporting the idea that STAT3 gain-of-function mutations can cause hyperactivation of the Th17 pathway and thereby contribute to autoimmunity.