Impaired TGF-β signaling in patients with active systemic lupus erythematosus is associated with an overexpression of IL-22.

摘要: The mechanisms leading to the disruption of self-tolerance in systemic lupus erythematosus (SLE) remain elusive. Herein, we aimed decipher molecular basis impaired response mononuclear cells TGF-β1. Smad3-pathway was explored on CD3+ lymphocytes either active or non SLE patients. An transcription TGF-β1 target genes demonstrated patients confirming that defect involves T and pointing its extrinsic nature. We further demonstrate did not result from an TGF-βRII expression Smad2/3 phosphorylation suggesting mechanism lies downstream translocation. Interestingly, TGF-1 signaling correlate with increased soluble membrane-bound IL-15. However, it associated overexpression IL-22. This suggests excessive activation AhR pathway (through UV radiations, infections, etc.) could lead inhibition immunosuppressive actions TGF-β thus disrupting immune homeostasis SLE. Collectively, our data suggest is disease activity provide new insights into pathogenesis since establish link between environmental factors aberrancies system usually described