{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:28:05Z","timestamp":1740137285985,"version":"3.37.3"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2014,7,7]],"date-time":"2014-07-07T00:00:00Z","timestamp":1404691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"publisher","award":["R01-GM065237","R01-GM036214"],"award-info":[{"award-number":["R01-GM065237","R01-GM036214"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A subset of Pts develops dysfunctional MO to inflammatory DC differentiation and immunosuppression. MDDC, a newly described DC subset, is pivotal in initiating antibacterial responses. Endogenous proteins are known to alter MO to MDDC differentiation. In particular, trauma-elevated TSP-1, a protein that is known to affect MO functions, could trigger MDDC differentiation defects. We hypothesized that TSP-1-deranged differentiation of inflammatory CD1a+MDDC would negatively alter activation of immune functions, thereby increasing the risk of postinjury infections. Post-trauma increased TSP-1 levels in patients' plasma and MO correlated with two distinct MDDC differentiation dysfunctions: the previously described decreased CD1a+DC yields but also, development of an immunoincompetent CD1a+MDDC. The Pts' development of Dysf DC correlated to increased infectious complications. TSP-1 triggered its inhibitory receptor, CD47, activating an inhibitory phosphatase, SHP-1. Increased pSHP-1, decreased antigen processing, and depressed T cell stimulation characterized Pt Dysf DC. TSP-1 mimics added during Cnt MDDC differentiation depressed CD1a+DC yields but more importantly, also induced defective CD1a+MDDC, reproducing Pts' MDDC differentiation dysfunctions. CD47 triggering during Cnt MDDC differentiation increased SHP-1 activation, inhibiting IL-4-induced STAT-6 activation (critical for CD1a+MDDC differentiation). SHP-1 inhibition during MDDC differentiation in the presence of TSP-1 mimics restored pSTAT-6 levels and CD1a+MDDC immunogenicity. Thus, postinjury-elevated TSP-1 can decrease CD1a+DC yields but more critically, also induces SHP-1 hyperactivity, deviating MDDC differentiation to defective CD1a+ inflammatory MDDCs by inhibiting STAT-6.<\/jats:p>","DOI":"10.1189\/jlb.4ma0214-077r","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T05:56:57Z","timestamp":1404799017000},"page":"797-807","source":"Crossref","is-referenced-by-count":12,"title":["Elevated postinjury thrombospondin 1\u2013CD47 triggering aids differentiation of patients' defective inflammatory CD1a+dendritic cells"],"prefix":"10.1093","volume":"96","author":[{"given":"Gautam","family":"Bandyopadhyay","sequence":"first","affiliation":[{"name":"Immunobiology and Stress Response Laboratory, Department of Surgery, University of Rochester Medical Center , Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjukta","family":"Bandyopadhyay","sequence":"additional","affiliation":[{"name":"Immunobiology and Stress Response Laboratory, Department of Surgery, University of Rochester Medical Center , Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul E","family":"Bankey","sequence":"additional","affiliation":[{"name":"Immunobiology and Stress Response Laboratory, Department of Surgery, University of Rochester Medical Center , Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol L","family":"Miller-Graziano","sequence":"additional","affiliation":[{"name":"Immunobiology and Stress Response Laboratory, Department of Surgery, University of Rochester Medical Center , Rochester, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,7,7]]},"reference":[{"key":"2023032708373355200_","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nri3149","article-title":"Transcriptional programming of the dendritic cell network","volume":"12","author":"Belz","year":"2012","journal-title":"Nat. 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