{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:30:57Z","timestamp":1780918257911,"version":"3.54.1"},"reference-count":28,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroimmunomodulation"],"published-print":{"date-parts":[[2020]]},"abstract":"<b><i>Background:<\/i><\/b> Previous work revealed the existence of a severe thymic atrophy with massive loss of immature CD4<sup>+<\/sup>CD8<sup>+<\/sup> thymocytes in animals developing insulin-dependent diabetes, chemically induced by alloxan. Furthermore, the intrathymic expression of chemokines, such as CXCL12, is changed in these animals, suggesting that cell migration-related patterns may be altered. One molecular interaction involved in normal thymocyte migration is that mediated by soluble semaphorin-3A and its cognate receptor neuropilin-1. <b><i>Objectives:<\/i><\/b> We investigated herein the expression and role of semaphorin-3A in the migratory responses of thymocytes from alloxan-induced diabetic mice. We characterized semaphorin-3A and its receptor, neuropilin-1, in thymuses from control and diabetic mice as well as semaphorin-3A-dependent migration of developing thymocytes in both control and diabetic animals. <b><i>Methods:<\/i><\/b> Diabetes was chemically induced after a single injection of alloxan in young adult BALB\/c mice. Thymocytes were excised from control and diabetic individuals and subjected to cytofluorometry for simultaneous detection of semaphorin-3A or neuropilin-1 in CD4\/CD8-defined subsets. Cell migration in response to semaphorin-3A was performed using cell migration transwell chambers. <b><i>Results:<\/i><\/b> Confirming previous data, we observed a severe decrease in the total numbers of thymocytes in diabetic mice, which comprised alterations in both immature (double-negative subpopulations) and mature CD4\/CD8-defined thymocyte subsets. These were accompanied by a decrease in the absolute numbers of semaphorin-3A-bearing thymocytes, comprising CD4<sup>\u2013<\/sup>CD8<sup>\u2013<\/sup>, CD4<sup>+<\/sup>CD8<sup>+<\/sup>, and CD4<sup>\u2013<\/sup>CD8<sup>+<\/sup> cells. Additionally, immature CD4<sup>\u2013<\/sup>CD8<sup>\u2013<\/sup> and CD4<sup>+<\/sup>CD8<sup>+<\/sup> developing T cells exhibited a decrease in the membrane density of semaphorin-3A. The relative and absolute numbers of neuropilin-1-positive thymocytes were also decreased in diabetic mouse thymocytes compared to controls, as seen in CD4<sup>\u2013<\/sup>CD8<sup>\u2013<\/sup>, CD4<sup>+<\/sup>CD8<sup>+<\/sup>, and CD4<sup>\u2013<\/sup>CD8<sup>+<\/sup> cell subpopulations. Functionally, we observed a decrease in the chemorepulsive role of semaphorin-3A, as revealed by transwell migration chambers. Such an effect was seen in all immature and mature thymocyte subsets. <b><i>Conclusions:<\/i><\/b> Taken together, our data clearly unravel a disruption in the normal cell migration pattern of developing thymocytes following chemically induced insulin-dependent diabetes, as ascertained by the altered migratory response to sempahorin-3A. In conceptual terms, it is plausible to think that such disturbances in the migration pattern of thymocytes from these diabetic animals may exert an impact in the cell-mediated immune response of these mice.<\/jats:p>","DOI":"10.1159\/000506054","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T22:00:34Z","timestamp":1583964034000},"page":"28-37","source":"Crossref","is-referenced-by-count":5,"title":["Semaphorin-3A-Related Reduction of Thymocyte Migration in Chemically Induced Diabetic Mice"],"prefix":"10.1159","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-3124","authenticated-orcid":false,"given":"Carolina","family":"Francelin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ieda","family":"Geniseli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Nagib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacy","family":"Gameiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson","family":"Savino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana","family":"Verinaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.23.090506.123547"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.168"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00347.x"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115715"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1003455"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.7.4639"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0709"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-202952"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700705104"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2008.03980.x"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0111031"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103405"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9051426"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.02.001"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1159\/000455936"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80369-4"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-3-211"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80535-8"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1159\/000329497"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1159\/000258708"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.11.025"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9425-6"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17257"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00686"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1038\/nri3198"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1007\/s10517-019-04346-x"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2012.11.015"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02828.x"}],"container-title":["Neuroimmunomodulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/506054","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/506054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:46:28Z","timestamp":1745423188000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000506054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,7,23]]},"published-print":{"date-parts":[[2020,7,30]]}},"URL":"https:\/\/doi.org\/10.1159\/000506054","archive":["Portico"],"relation":{},"ISSN":["1021-7401","1423-0216"],"issn-type":[{"value":"1021-7401","type":"print"},{"value":"1423-0216","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020]]}}}