{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:16:57Z","timestamp":1761844617742,"version":"3.37.3"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,2,8]],"date-time":"2016-02-08T00:00:00Z","timestamp":1454889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"U.S. National Institutes of Health National Eye Institute","award":["R01EY021798","P30EY005722"],"award-info":[{"award-number":["R01EY021798","P30EY005722"]}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re-exposure, or secondary responses. However, molecular cues by dendritic cells underpinning allergic T cell response levels and the impact that this control has on consequent severity of allergic disease are poorly understood. Here, we show that a deficiency in thrombospondin-1, a matricellular protein known to affect immune function, has subsequent effects on downstream T cell responses during allergy, as revealed in an established mouse model of allergic eye disease. More specifically, we demonstrate that a thrombospondin-1 deficiency specific to dendritic cells leads to heightened secondary T cell responses and consequent clinical disease. Interestingly, whereas thrombospondin-1-deficient dendritic cells augmented activity of allergen-primed T cells, this increase was not recapitulated with na\u00efve T cells in vitro. The role of dendritic cell-derived thrombospondin-1 in regulating secondary allergic T cell responses was confirmed in vivo, as local transfer of thrombospondin-1-sufficient dendritic cells to the ocular mucosa of thrombospondin-1 null hosts prevented the development of augmented secondary T cell responses and heightened allergic eye disease clinical responses. Finally, we demonstrate that topical instillation of thrombospondin-1-derived peptide reduces T cell activity and clinical progression of allergic eye disease. Taken together, this study reveals an important modulatory role of dendritic cell-derived thrombospondin-1 on secondary allergic T cell responses and suggests the possible dysregulation of dendritic cell-derived thrombospondin-1 expression as a factor in allergic eye disease severity.<\/jats:p>","DOI":"10.1189\/jlb.3a0815-357rr","type":"journal-article","created":{"date-parts":[[2016,2,9]],"date-time":"2016-02-09T03:09:08Z","timestamp":1454987348000},"page":"371-380","source":"Crossref","is-referenced-by-count":13,"title":["Secondary allergic T cell responses are regulated by dendritic cell-derived thrombospondin-1 in the setting of allergic eye disease"],"prefix":"10.1093","volume":"100","author":[{"given":"R E","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Duke University School of Medicine , Durham, North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N J","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University School of Medicine , Durham, North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Khandelwal","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S L","family":"Schlereth","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H S","family":"Lee","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Masli","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston University Medical Center , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D R","family":"Saban","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Duke University School of Medicine , Durham, North Carolina , USA"},{"name":"Department of Immunology, Duke University School of Medicine , Durham, North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,2,8]]},"reference":[{"key":"2023011710412922500_B1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1824-7288-39-18","article-title":"Allergic conjunctivitis: a comprehensive review of the literature","volume":"39","author":"La Rosa","year":"2013","journal-title":"Ital. 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