Rôle de PKR dans la physiopathologie du lupus
(2018)
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- Abstract
- Systemic lupus erythematosus is a heterogeneous autoimmune disease and understanding the physiopathology is necessary to improve treatments. In this work, we study the role of PKR in the lupus physiopathology. In fact, once activated, this protein produces interferon-α, the key cytokine of the disease. With our experiments, we show that PKR is overexpressed and spontaneously activated in lupus patients. We then show that the inhibition of PKR on blood cells of lupus patients induces an inhibition of the production of interferon-induced genes and immunoglobulins. We also show that 6-mercaptopurine, the active metabolite of azathioprine, a drug whose mechanism of action is not fully understood, is also a PKR inhibitor. Finally, a lupus murine model in which we inactivated PKR, shows that this protein plays a role in the differentiation of B cells producing autoantibodies that are pathogenic for the kidney. Our results are consistent with a key role of PKR in the physiopathology of the disease.
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De Groof, A. (2018). Rôle de PKR dans la physiopathologie du lupus. https://hdl.handle.net/2078.5/48000