A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice
Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β cells by autoantigen-reactive diabetogenic cells. Antigen-specific therapies using islet autoantigens for restoring immune tolerance have emerged as promising approaches for the treatment of T1D but have been un...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2019/9430473 |
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| author | Hidetoshi Akimoto Emi Fukuda-Kawaguchi Omar Duramad Yasuyuki Ishii Kazunari Tanabe |
| author_facet | Hidetoshi Akimoto Emi Fukuda-Kawaguchi Omar Duramad Yasuyuki Ishii Kazunari Tanabe |
| author_sort | Hidetoshi Akimoto |
| collection | DOAJ |
| description | Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β cells by autoantigen-reactive diabetogenic cells. Antigen-specific therapies using islet autoantigens for restoring immune tolerance have emerged as promising approaches for the treatment of T1D but have been unsuccessful in humans. Herein, we report that RGI-3100-iB, a novel liposomal formulation carrying both α-galactosylceramide (α-GalCer), which is a representative ligand for invariant natural killer T (iNKT) cells, and insulin B chain 9–23 peptide, which is an epitope for CD4+ T cells, could induce the accumulation of regulatory T cells (Tregs) in islets in a peptide-dependent manner, followed by the remarkable prevention of diabetes onset in nonobese diabetic (NOD) mice. While multiple administrations of a monotherapy using either α-GalCer or insulin B peptide in a liposomal formulation was confirmed to delay/prevent T1D in NOD mice, RGI-3100-iB synergistically enhanced the prevention effect of each monotherapy and alleviated insulitis in NOD mice. Immunopathological analysis showed that Foxp3+ Tregs accumulated in the islets in RGI-3100-iB-treated mice. Cotransfer of diabetogenic T cells and splenocytes of NOD mice treated with RGI-3100-iB, but not liposomal α-GalCer encapsulating an unrelated peptide, to NOD-SCID mice resulted in the prevention of diabetes and elevation of Foxp3 mRNA expression in the islets. These data indicate that the migration of insulin B-peptide-specific Tregs to islet of NOD mice that are involved in the suppression of pathogenic T cells related to diabetes onset and progression could be enhanced by the administration of liposomes containing α-GalCer and insulin B peptide. |
| format | Article |
| id | doaj-art-3a33de59e5914dbeb4b7ad6ad7280e04 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-3a33de59e5914dbeb4b7ad6ad7280e042025-02-03T05:59:51ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/94304739430473A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic MiceHidetoshi Akimoto0Emi Fukuda-Kawaguchi1Omar Duramad2Yasuyuki Ishii3Kazunari Tanabe4Research Division, REGiMMUNE Corporation, 35-3 Nihonbashi Hakozaki-cho, BRICK GATE 5F, Chuou-Ku, Tokyo 103-0015, JapanResearch Division, REGiMMUNE Corporation, 35-3 Nihonbashi Hakozaki-cho, BRICK GATE 5F, Chuou-Ku, Tokyo 103-0015, JapanResearch Division, REGiMMUNE Inc, 820 Heinz Ave, Berkeley, CA 94710, USAResearch Division, REGiMMUNE Corporation, 35-3 Nihonbashi Hakozaki-cho, BRICK GATE 5F, Chuou-Ku, Tokyo 103-0015, JapanDepartment of Urology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-Ku, Tokyo 162-8666, JapanType 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β cells by autoantigen-reactive diabetogenic cells. Antigen-specific therapies using islet autoantigens for restoring immune tolerance have emerged as promising approaches for the treatment of T1D but have been unsuccessful in humans. Herein, we report that RGI-3100-iB, a novel liposomal formulation carrying both α-galactosylceramide (α-GalCer), which is a representative ligand for invariant natural killer T (iNKT) cells, and insulin B chain 9–23 peptide, which is an epitope for CD4+ T cells, could induce the accumulation of regulatory T cells (Tregs) in islets in a peptide-dependent manner, followed by the remarkable prevention of diabetes onset in nonobese diabetic (NOD) mice. While multiple administrations of a monotherapy using either α-GalCer or insulin B peptide in a liposomal formulation was confirmed to delay/prevent T1D in NOD mice, RGI-3100-iB synergistically enhanced the prevention effect of each monotherapy and alleviated insulitis in NOD mice. Immunopathological analysis showed that Foxp3+ Tregs accumulated in the islets in RGI-3100-iB-treated mice. Cotransfer of diabetogenic T cells and splenocytes of NOD mice treated with RGI-3100-iB, but not liposomal α-GalCer encapsulating an unrelated peptide, to NOD-SCID mice resulted in the prevention of diabetes and elevation of Foxp3 mRNA expression in the islets. These data indicate that the migration of insulin B-peptide-specific Tregs to islet of NOD mice that are involved in the suppression of pathogenic T cells related to diabetes onset and progression could be enhanced by the administration of liposomes containing α-GalCer and insulin B peptide.http://dx.doi.org/10.1155/2019/9430473 |
| spellingShingle | Hidetoshi Akimoto Emi Fukuda-Kawaguchi Omar Duramad Yasuyuki Ishii Kazunari Tanabe A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice Journal of Diabetes Research |
| title | A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice |
| title_full | A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice |
| title_fullStr | A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice |
| title_full_unstemmed | A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice |
| title_short | A Novel Liposome Formulation Carrying Both an Insulin Peptide and a Ligand for Invariant Natural Killer T Cells Induces Accumulation of Regulatory T Cells to Islets in Nonobese Diabetic Mice |
| title_sort | novel liposome formulation carrying both an insulin peptide and a ligand for invariant natural killer t cells induces accumulation of regulatory t cells to islets in nonobese diabetic mice |
| url | http://dx.doi.org/10.1155/2019/9430473 |
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