{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:43:34Z","timestamp":1788975814889,"version":"build-2803163510"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"31","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,8,2]]},"abstract":"<jats:p>Autoimmune diseases, such as rheumatoid arthritis, frequently target one major tissue\/organ despite the systemic nature of the immune response. This is particularly perplexing in the case of ubiquitously distributed antigens invoked in arthritis induction. We reasoned that selective targeting of the synovial joints in autoimmune arthritis might be due in part to the unique attributes of the joint vasculature. We examined this proposition using the adjuvant-induced arthritis model of human rheumatoid arthritis, and profiled the synovial vasculature using ex vivo and in vivo screening of a defined phage peptide-display library. We identified phage that preferentially homed to the inflamed joints. The corresponding synthetic peptides showed binding to the joint-derived endothelial cells, as well as specificity in inhibiting binding of the respective phage to the synovial vasculature. Intriguingly, the treatment of arthritic rats with one such peptide resulted in efficient inhibition of the progression of arthritis. The suppression of arthritis was attributable in part to the peptide-induced reduction of T-cell trafficking into the joints and the inhibition of angiogenesis. This peptide differed in sequence, in receptor binding specificity, and in angiogenesis\/inflammation-related cell signaling from the previously characterized arginine-glycine-aspartic acid\u2013containing peptide. Thus, our study reveals joint-homing peptides that can be further exploited for the selective delivery of antiarthritic agents into the inflamed joints to enhance their efficacy while reducing systemic toxicity, and also for examining intricacies of the pathogenesis of arthritis. This approach can be customized for application to other organ-specific autoimmune diseases as well.<\/jats:p>","DOI":"10.1073\/pnas.1103569108","type":"journal-article","created":{"date-parts":[[2011,7,18]],"date-time":"2011-07-18T23:35:45Z","timestamp":1311032145000},"page":"12857-12862","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":38,"title":["Peptides targeting inflamed synovial vasculature attenuate autoimmune arthritis"],"prefix":"10.1073","volume":"108","author":[{"given":"Ying-Hua","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Rajaiah","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erkki","family":"Ruoslahti","sequence":"additional","affiliation":[{"name":"Vascular Mapping Laboratory, Center for Nanomedicine, Sanford-Burnham Medical Research Institute at University of California at Santa Barbara, Santa Barbara, CA 93106; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal D.","family":"Moudgil","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;"},{"name":"Division of Rheumatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,7,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2008.01.003"},{"key":"e_1_3_3_2_2","first-page":"281","article-title":"Autoantigens and immune pathways in rheumatoid arthritis","volume":"22","author":"Corrigall VM","year":"2002","unstructured":"VM Corrigall, GS Panayi, Autoantigens and immune pathways in rheumatoid arthritis. 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