The molecular mechanisms underlying the autoimmune disorder systemic lupus erythematosus (SLE) remain unknown. Here, Wang et. al. report that SH2 domain-containing protein tyrosine phosphatase (SHP2) activity is increased in lupus-prone MRL-lpr mouse spleen isolates and in peripheral blood mononuclear cells isolated from lupus patients. In MRL-lpr mice, SHP2 inhibition using the hydroxyindole carboxylic acid-based inhibitor 11a-1 increased life span, improved kidney function, reduced splenomegaly, diminished skin lesions, and also decreased T cell proliferation and production of SLE-associated cytokines. Moreover, 11a-1 reduced proliferation and cytokine production of cultured human lupus T cells.
References
Wang, J. et al. Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus. J. Clin. Inves. 126, 2077–2092 (2016)
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Crunkhorn, S. Reversing systemic lupus erythematosus. Nat Rev Drug Discov 15, 456 (2016). https://doi.org/10.1038/nrd.2016.128
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DOI: https://doi.org/10.1038/nrd.2016.128