{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:25:09Z","timestamp":1761513909237,"version":"3.38.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Rheumatoid arthritis is an autoimmune disorder characterized by T cell dysregulation. We have shown that an altered peptide ligand (A9) activates T cells to use an alternate signaling pathway that is dependent on FcR\u03b3 and spleen tyrosine kinase, resulting in downregulation of inflammation. In the experiments described in this study, we have attempted to determine the molecular basis of this paradox. Three major Src family kinases found in T cells (Lck, Fyn, and Lyn) were tested for activation following stimulation by A9\/I-Aq. Unexpectedly we found they are not required for T cell functions induced by A9\/I-Aq, nor are they required for APL stimulation of cytokines. On the other hand, the induction of the second messenger inositol trisphosphate and the mobilization of calcium are clearly triggered by the APL A9\/I-Aq stimulation and are required for cytokine production, albeit the cytokines induced are different from those produced after activation of the canonical pathway. DBA\/1 mice doubly deficient in IL-4 and IL-10 were used to confirm that these two cytokines are important for the APL-induced attenuation of arthritis. These studies provide a basis for exploring the effectiveness of analog peptides and the inhibitory T cells they induce as therapeutic tools for autoimmune arthritis.<\/jats:p>","DOI":"10.4049\/jimmunol.1600771","type":"journal-article","created":{"date-parts":[[2016,11,12]],"date-time":"2016-11-12T03:44:19Z","timestamp":1478922259000},"page":"4569-4575","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of the Syk-Dependent T Cell Signaling Response to an Altered Peptide"],"prefix":"10.1093","volume":"197","author":[{"given":"Jeoung-Eun","family":"Park","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center , Memphis TN 38163"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6123-4722","authenticated-orcid":false,"given":"Jeffrey A","family":"Rotondo","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center , Memphis TN 38163"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3548-3458","authenticated-orcid":false,"given":"David L","family":"Cullins","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center , Memphis TN 38163"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9260-7963","authenticated-orcid":false,"given":"David D","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center , Memphis TN 38163"},{"name":"Research Service, Veterans Affairs Medical Center , Memphis TN 38104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ae-Kyung","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center , Memphis TN 38163"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M","family":"Stuart","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center , Memphis TN 38163"},{"name":"Research Service, Veterans Affairs Medical Center , Memphis TN 38104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew H","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center , Memphis TN 38163"},{"name":"Research Service, Veterans Affairs Medical Center , Memphis TN 38104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda K","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Tennessee Health Science Center , Memphis TN 38163"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"2025030618360692300_r1","doi-asserted-by":"crossref","first-page":"v3","DOI":"10.1093\/rheumatology\/kes113","article-title":"Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis","volume":"51","author":"Choy","year":"2012","journal-title":"Rheumatology (Oxford)"},{"key":"2025030618360692300_r2","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.4049\/jimmunol.160.7.3135","article-title":"Characterization of signal transduction through the TCR-zeta chain following T cell stimulation with analogue peptides of type II collagen 260-267","volume":"160","author":"Tang","year":"1998","journal-title":"J. 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