Reduced Suppressor of Cytokine Signaling-1 levels in SLE patients correlates to enhanced STAT1 activation

• Published in: The Journal of immunology (1950) 2016-05, Vol.196 (1_Supplement), p.124-124.23
• Main Authors: Sukka-Ganesh, BhagyaLaxmi, Li, Yi, Reeves, Westley H, Larkin, Joseph
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.124.23

Systemic Lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder with unknown etiology. Although the specific events dictating SLE pathology remain unclear, abundant evidence indicates a critical role for dysregulated cytokine signaling in disease progression. Notably, the suppressor of cytokine signaling (SOCS) family of intracellular proteins, in particular the kinase inhibitory region (KIR) bearing SOCS1 and SOCS3, play a critical role in regulating cytokine signaling. Here in this foundational study, we test the hypothesis that regulation of cytokine signaling in SLE patients may be perturbed by a lack of KIR bearing SOCS1 and SOCS3. We analyzed 34 SLE patients, segregated by disease activity (SLEDAI) and prednisone treatment, in comparison with 11 healthy controls. Real time RT-PCR and Western blot analysis showed significant reductions in SOCS1 and SOCS3 in PMBC’s of SLE patients by both mRNA and protein expression when compared to controls. Notably, decreased SOCS1, but not SOCS3 protein levels in the SLE patients were inversely correlated to activation of STAT1, but not Erk 1/2 or Akt. Notably, the inverted SOCS1/pSTAT1 ratio correlated to significantly enhanced MHC class II levels amongst SLE patients. These studies represent a critical first step in implicating a role of SOCS1 and SOCS3 deficiencies in the progression of human SLE, providing impetus for the performance for a larger multi-centered examination. Finally, these studies point to the possibility that peptides, previously shown to mimic SOCS signaling and inhibit rodent autoimmune disease, may have efficacy in the treatment of human SLE.