{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:56:05Z","timestamp":1763535365967},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":2171,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH","award":["JDRF 11-2007-825","NIH DK078863","UL1 TR000064"],"award-info":[{"award-number":["JDRF 11-2007-825","NIH DK078863","UL1 TR000064"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,2,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Granulocyte colony-stimulating factor (G-CSF) has been used to restore immune competence following chemoablative cancer therapy and to promote immunological tolerance in certain settings of autoimmunity. Therefore, we tested the potential of G-CSF to impact type 1 diabetes (T1D) progression in patients with recent-onset disease [n = 14; n = 7 (placebo)] and assessed safety, efficacy and mechanistic effects on the immune system. We hypothesized that pegylated G-CSF (6 mg administered subcutaneously every 2 weeks for 12 weeks) would promote regulatory T cell (Treg) mobilization to a degree capable of restoring immunological tolerance, thus preventing further decline in C-peptide production. Although treatment was well tolerated, G-CSF monotherapy did not affect C-peptide production, glycated haemoglobin (HbA1c) or insulin dose. Mechanistically, G-CSF treatment increased circulating neutrophils during the 12-week course of therapy (P &amp;lt; 0\u00b701) but did not alter Treg frequencies. No effects were observed for CD4+ : CD8+ T cell ratio or the ratio of naive : memory (CD45RA+\/CD45RO+) CD4+ T cells. As expected, manageable bone pain was common in subjects receiving G-CSF, but notably, no severe adverse events such as splenomegaly occurred. This study supports the continued exploration of G-CSF and other mobilizing agents in subjects with T1D, but only when combined with immunodepleting agents where synergistic mechanisms of action have previously demonstrated efficacy towards the preservation of C-peptide.<\/jats:p>","DOI":"10.1111\/cei.12731","type":"journal-article","created":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T08:35:12Z","timestamp":1444811712000},"page":"350-357","source":"Crossref","is-referenced-by-count":12,"title":["Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes"],"prefix":"10.1093","volume":"183","author":[{"given":"M J","family":"Haller","sequence":"first","affiliation":[{"name":"Departments of Pediatric Endocrinology, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M A","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Endocrinology, University of Florida, Gainesville, FL, USA"},{"name":"Immunology, Pathology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C H","family":"Wasserfall","sequence":"additional","affiliation":[{"name":"Immunology, Pathology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T M","family":"Brusko","sequence":"additional","affiliation":[{"name":"Immunology, Pathology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C E","family":"Mathews","sequence":"additional","affiliation":[{"name":"Immunology, Pathology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Hulme","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Cintron","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Endocrinology, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Shuster","sequence":"additional","affiliation":[{"name":"Health Outcomes and Policy, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"McGrail","sequence":"additional","affiliation":[{"name":"Immunology, Pathology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Posgai","sequence":"additional","affiliation":[{"name":"Immunology, Pathology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Schatz","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Endocrinology, University of Florida, Gainesville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,12,7]]},"reference":[{"key":"2021111804091047400_cei12731-bib-0001","doi-asserted-by":"crossref","first-page":"979","DOI":"10.2337\/dc15-0144","article-title":"Current concepts on the pathogenesis of type 1 diabetes \u2013 considerations for attempts to prevent and reverse the disease","volume":"38","author":"Atkinson","year":"2015","journal-title":"Diabetes 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