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1404 A peptide mimetic of the kinase inhibitory region of suppressor of cytokine signaling-1 attenuates lymphocyte activation and lupus progression in MRL/Lpr lupus model
  1. Jatin Sharma1,
  2. Teresa D Collins1,
  3. Tracoyia Roach2,
  4. Shiwangi Mishra1,
  5. Brandon K Lam1,
  6. Zaynab Sidi Mohamed1,
  7. Antia E Veal1,
  8. Timothy B Polk1,
  9. Amari Jones1,
  10. Caleb Cornaby2,
  11. Mohammed I Haider1,
  12. Leilani Zeumer-Spataro2,
  13. Howard M Johnson1,
  14. Laurence M Morel2 and
  15. Joseph Larkin1
  1. 1Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
  2. 2Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA


Background Lupus progression is driven by the aberrant activation of T and B lymphocytes which promote a dysregulated cytokine milieu and produce pathogenic antibodies. Many cytokines, including interferon gamma (IFN-γ), utilize the janus kinase/signal transduction and activation of transcription (JAK/STAT) pathway for signal propagation. Suppressor of Cytokine Signaling-1 (SOCS-1) is an inducible, intracellular protein which regulates the JAK/STAT pathway and IFNγ signaling. We have previously shown that a peptide mimicking the kinase inhibitory region of SOCS1 (SOCS1-KIR) inhibited IFN-γ signaling and inflammation-mediated disease progression.

Using MRL/lpr mice, which spontaneously develop SLE-like disease, we test the hypothesis that SOCS1-KIR administration inhibits T and B lymphocyte activation leading to an amelioration in lupus pathology.

Methods Female MRL/lpr mice received intraperitoneal injections of SOCS1-KIR peptide, or PBS carrier, 3 times per week and were monitored for lupus-like disease progression. Disease progression was based on the presence of skin lesions, lymphadenopathy, overall body score, and proteinuria. Peripheral blood, lymph nodes, and spleen was evaluated for peptide-mediated changes in lymphocyte populations by flow cytometry and qPCR. ELISA and western blot analysis were also employed to assess changes in lymphocyte activation. Finally, peptide mediated changes in renal pathology were analyzed.

Results We show that intraperitoneal administration of SOCS1-KIR reduced the frequency, activation, and cytokine production of memory CD8+ and CD4+ T lymphocytes within the peripheral blood, spleen, and lymph nodes of treated mice. In addition, administration of SOCS1-KIR mimetic peptide treatment reduced lymphadenopathy, delayed the development and severity of skin lesions, reduced autoantibody production, and lupus associated kidney destruction. On a cellular level, SOCS1-KIR administration enhanced Foxp3 expression in both total splenic Tregs and follicular Tregs (figure 1). In addition, SOCS1-KIR treatment reduced the frequency of GL7+ germinal center enriched B cells and CD80+ leukocytes, which may potentially activate T lymphocytes.

Abstract 1404 Figure 1

Graphical representation of the study design and results

Conclusion Together, these data show that SOCS1-KIR treatment was effective in reducing auto-reactive lymphocyte effector functions and suggest that therapeutic targeting of the SOCS1 pathway through peptide administration may have efficacy in mitigating lupus progression.

Acknowledgement We thank Mr. Benson and Dr. Moneypenny for flow cytometry assistance, UF animal care, and Drs. Hoffman and Wilson for technical expertise. This study was supported by the Lupus Research Institute, National Psoriasis Foundation, a BD Biosciences Research Grant, NIH/NCATS Clinical and Translational Science Awards TL1 TR000066 and UL1TR000064, NIH/NIAID subaward U01AI101990 and The Mcknight Fellowship Foundation.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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