| Autor: |
Sharma J; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Collins TD; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Roach T; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA., Mishra S; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Lam BK; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Mohamed ZS; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Veal AE; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Polk TB; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Jones A; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Cornaby C; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA., Haider MI; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Zeumer-Spataro L; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA., Johnson HM; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA., Morel LM; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, 32610, USA., Larkin J 3rd; Department of Microbiology & Cell Science, University of Florida, Museum Road Building 981, PO Box 110700, Gainesville, FL, 32611, USA. jlarkin3@ufl.edu. |
| Abstrakt: |
Autoimmune diseases are driven largely by a pathogenic cytokine milieu produced by aberrantly activated lymphocytes. Many cytokines, including interferon gamma (IFN-γ), utilize the JAK/STAT pathway for signal propagation. Suppressor of Cytokine Signaling-1 (SOCS1) is an inducible, intracellular protein that regulates IFN-γ signaling by dampening JAK/STAT signaling. Using Fas deficient, MRL/MpJ-Fas lpr /J (MRL/lpr) mice, which develop lupus-like disease spontaneously, we tested the hypothesis that a peptide mimic of the SOCS1 kinase inhibitory region (SOCS1-KIR) would inhibit lymphocyte activation and modulate lupus-associated pathologies. Consistent with in vitro studies, SOCS1-KIR intraperitoneal administration reduced the frequency, activation, and cytokine production of memory CD8 + and CD4 + T lymphocytes within the peripheral blood, spleen, and lymph nodes. In addition, SOCS1-KIR administration reduced lymphadenopathy, severity of skin lesions, autoantibody production, and modestly reduced kidney pathology. On a cellular level, peritoneal SOCS1-KIR administration enhanced Foxp3 expression in total splenic and follicular regulatory T cells, reduced the effector memory/naïve T lymphocyte ratio for both CD4 + and CD8 + cells, and reduced the frequency of GL7 + germinal center enriched B cells. Together, these data show that SOCS1-KIR treatment reduced auto-reactive lymphocyte effector functions and suggest that therapeutic targeting of the SOCS1 pathway through peptide administration may have efficacy in mitigating autoimmune pathologies. |
