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Many cytokines, including interferon gamma (IFN-\u03b3), utilize the JAK\/STAT pathway for signal propagation. Suppressor of Cytokine Signaling-1 (SOCS1) is an inducible, intracellular protein that regulates IFN-\u03b3 signaling by dampening JAK\/STAT signaling. Using Fas deficient, MRL\/MpJ-Fas<jats:sup>lpr<\/jats:sup>\/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<jats:sup>+<\/jats:sup>and CD4<jats:sup>+<\/jats:sup>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\/na\u00efve T lymphocyte ratio for both CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>cells, and reduced the frequency of GL7<jats:sup>+<\/jats:sup>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.<\/jats:p>","DOI":"10.1038\/s41598-021-86017-4","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T16:47:41Z","timestamp":1616086061000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Suppressor of cytokine signaling-1 mimetic peptides attenuate lymphocyte activation in the MRL\/lpr mouse autoimmune model"],"prefix":"10.1038","volume":"11","author":[{"given":"Jatin","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa D.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracoyia","family":"Roach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwangi","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon K.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaynab Sidi","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antia E.","family":"Veal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Polk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amari","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Cornaby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed I.","family":"Haider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilani","family":"Zeumer-Spataro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard M.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence M.","family":"Morel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Joseph","family":"Larkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"86017_CR1","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/nrrheum.2017.43","volume":"13","author":"L Morel","year":"2017","unstructured":"Morel, L. 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