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Suppressor of cytokine signaling-1 mimetic peptides attenuate lymphocyte activation in the MRL/lpr mouse autoimmune model.
Suppressor of cytokine signaling-1 mimetic peptides attenuate lymphocyte activation in the MRL/lpr mouse autoimmune model.
- Source :
-
Scientific reports [Sci Rep] 2021 Mar 18; Vol. 11 (1), pp. 6354. Date of Electronic Publication: 2021 Mar 18. - Publication Year :
- 2021
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Abstract
- 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 <superscript>lpr</superscript> /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 <superscript>+</superscript> and CD4 <superscript>+</superscript> 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 <superscript>+</superscript> and CD8 <superscript>+</superscript> cells, and reduced the frequency of GL7 <superscript>+</superscript> 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.
- Subjects :
- Animals
Autoimmune Diseases genetics
Autoimmune Diseases immunology
Autoimmune Diseases pathology
B-Lymphocytes drug effects
Biomimetics
CD4-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes drug effects
Cytokines genetics
Interferon-gamma genetics
Janus Kinases genetics
Lupus Erythematosus, Systemic genetics
Lupus Erythematosus, Systemic immunology
Lymph Nodes drug effects
Lymph Nodes immunology
Lymphocytes drug effects
Lymphocytes immunology
Mice, Inbred MRL lpr
Peptides chemical synthesis
STAT Transcription Factors genetics
Spleen drug effects
Spleen immunology
Suppressor of Cytokine Signaling 1 Protein pharmacology
T-Lymphocytes, Regulatory drug effects
T-Lymphocytes, Regulatory immunology
fas Receptor genetics
Mice
Autoimmune Diseases drug therapy
Forkhead Transcription Factors genetics
Lupus Erythematosus, Systemic drug therapy
Peptides pharmacology
Suppressor of Cytokine Signaling 1 Protein genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33737712
- Full Text :
- https://doi.org/10.1038/s41598-021-86017-4