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This is called oral tolerance and is capable of suppressing autoimmune type 1 diabetes (T1D). However, the process by which the CTB-insulin (CTB-INS) protein works as a therapy for T1D<jats:italic>in vivo<\/jats:italic>remains unclear. Here, we successfully expressed a green fluorescent protein- (GFP-) tagged CTB-Ins (CTB-Ins-GFP) fusion protein in silkworms in a pentameric form that retained the native ability to activate the mechanism. Oral administration of the CTB-Ins-GFP protein induced special tolerance, delayed the development of diabetic symptoms, and suppressed T1D onset in nonobese diabetic (NOD) mice. Moreover, it increased the numbers of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup>T regulatory (Treg) cells in peripheral lymph tissues and affected the biological activity of spleen cells. This study demonstrated that the CTB-Ins-GFP protein produced in silkworms acted as an oral protein vaccine, inducing immunological tolerance involving CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup>Treg cells in treating T1D.<\/jats:p>","DOI":"10.1155\/2011\/831704","type":"journal-article","created":{"date-parts":[[2011,6,30]],"date-time":"2011-06-30T21:41:44Z","timestamp":1309470104000},"page":"1-14","source":"Crossref","is-referenced-by-count":10,"title":["Protection against Autoimmune Diabetes by Silkworm-Produced GFP-Tagged CTB-Insulin Fusion Protein"],"prefix":"10.1155","volume":"2011","author":[{"given":"Qiaohong","family":"Meng","sequence":"first","affiliation":[{"name":"Institute of Biochemistry, College of Life Sciences, Zhejiang University (Zijingang Campus), 388 Yuhangtang Road, Hangzhou 310058, 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