{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T03:32:21Z","timestamp":1785123141753,"version":"3.55.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 114932"],"award-info":[{"award-number":["MOP 114932"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Protective immunity to cutaneous leishmaniasis is mediated by IFN-\u03b3\u2013secreting CD4+ Th1 cells. IFN-\u03b3 binds to its receptor on Leishmania-infected macrophages, resulting in their activation, production of NO, and subsequent destruction of parasites. This study investigated the role of Semaphorin 3E (Sema3E) in host immunity to Leishmania major infection in mice. We observed a significant increase in Sema3E expression at the infection site at different timepoints following L. major infection. Sema3E-deficient (Sema3E knockout [KO]) mice were highly resistant to L. major infection, as evidenced by significantly (p &amp;lt; 0.05\u20130.01) reduced lesion sizes and lower parasite burdens at different times postinfection when compared with their infected wild-type counterpart mice. The enhanced resistance of Sema3E KO mice was associated with significantly (p &amp;lt; 0.05) increased IFN-\u03b3 production by CD4+ T cells. CD11c+ cells from Sema3E KO mice displayed increased expression of costimulatory molecules and IL-12p40 production following L. major infection and were more efficient at inducing the differentiation of Leishmania-specific CD4+ T cells to Th1 cells than their wild-type counterpart cells. Furthermore, purified CD4+ T cells from Sema3E KO mice showed increased propensity to differentiate into Th1 cells in vitro, and this was significantly inhibited by the addition of recombinant Sema3E in vitro. These findings collectively show that Sema3E is a negative regulator of protective CD4+ Th1 immunity in mice infected with L. major and suggest that its neutralization may be a potential therapeutic option for treating individuals suffering from cutaneous leishmaniasis.<\/jats:p>","DOI":"10.4049\/jimmunol.2000516","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T18:08:25Z","timestamp":1608746905000},"page":"588-598","source":"Crossref","is-referenced-by-count":9,"title":["Semaphorin 3E Promotes Susceptibility to <i>Leishmania major<\/i> Infection in Mice by Suppressing CD4+ Th1 Cell Response"],"prefix":"10.1093","volume":"206","author":[{"given":"Nnamdi M","family":"Ikeogu","sequence":"first","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chidalu A","family":"Edechi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 3P5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3441-0051","authenticated-orcid":false,"given":"Gloria N","family":"Akaluka","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Feiz-Barazandeh","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1934-1337","authenticated-orcid":false,"given":"Romaniya R","family":"Zayats","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3032-4335","authenticated-orcid":false,"given":"Enitan S","family":"Salako","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-7961","authenticated-orcid":false,"given":"Somtochukwu S","family":"Onwah","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5592-7095","authenticated-orcid":false,"given":"Chukuwunonso","family":"Onyilagha","sequence":"additional","affiliation":[{"name":"National Centre for Foreign Animal Disease, Canadian Food Inspection Agency , Winnipeg, Manitoba R3E 3M4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9780-2936","authenticated-orcid":false,"given":"Lianyu","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-2726","authenticated-orcid":false,"given":"Thomas T","family":"Murooka","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1265-6560","authenticated-orcid":false,"given":"Abdelilah S","family":"Gounni","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jude E","family":"Uzonna","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba R3E 0T5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"2025022610331739900_r1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nri.2016.72","article-title":"Cutaneous leishmaniasis: immune responses in protection and pathogenesis","volume":"16","author":"Scott","year":"2016","journal-title":"Nat. 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