The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse
Regulatory T lymphocytes expressing the transcription factor Foxp3 (Tregs) play an important role in the prevention of autoimmune diseases and other immunopathologies. Aberrations in Treg-mediated immunosuppression are therefore thought to be involved in the development of autoimmune pathologies, bu...
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| Format: | Article |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1358459/full |
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| author | Jérémy C. Santamaria Sylvia Vuillier Ariel O. Galindo-Albarrán Sarah Castan Claire Detraves Olivier P. Joffre Paola Romagnoli Joost P. M. van Meerwijk |
| author_facet | Jérémy C. Santamaria Sylvia Vuillier Ariel O. Galindo-Albarrán Sarah Castan Claire Detraves Olivier P. Joffre Paola Romagnoli Joost P. M. van Meerwijk |
| author_sort | Jérémy C. Santamaria |
| collection | DOAJ |
| description | Regulatory T lymphocytes expressing the transcription factor Foxp3 (Tregs) play an important role in the prevention of autoimmune diseases and other immunopathologies. Aberrations in Treg-mediated immunosuppression are therefore thought to be involved in the development of autoimmune pathologies, but few have been documented. Recent reports indicated a central role for Tregs developing during the neonatal period in the prevention of autoimmune pathology. We therefore investigated the development of Tregs in neonatal NOD mice, an important animal model for autoimmune type 1 diabetes. Surprisingly, we found that, as compared with seven other commonly studied inbred mouse strains, in neonatal NOD mice, exceptionally large proportions of developing Tregs express high levels of GITR and PD-1. The latter phenotype was previously associated with high Treg autoreactivity in C57BL/6 mice, which we here confirm for NOD animals. The proportions of newly developing GITRhighPD-1+ Tregs rapidly drop during the first week of age. A genome-wide genetic screen indicated the involvement of several diabetes susceptibility loci in this trait. Analysis of a congenic mouse strain confirmed that Idd5 contributes to the genetic control of GITRhighPD-1+ Treg development in neonates. Our data thus demonstrate an intriguing and paradoxical correlation between an idiosyncrasy in Treg development in NOD mice and their susceptibility to type 1 diabetes. |
| first_indexed | 2024-03-08T04:02:29Z |
| format | Article |
| id | doaj.art-4d76320316e444f081f86a653726f9bd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T04:02:29Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4d76320316e444f081f86a653726f9bd2024-02-09T11:02:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13584591358459The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouseJérémy C. SantamariaSylvia VuillierAriel O. Galindo-AlbarránSarah CastanClaire DetravesOlivier P. JoffrePaola RomagnoliJoost P. M. van MeerwijkRegulatory T lymphocytes expressing the transcription factor Foxp3 (Tregs) play an important role in the prevention of autoimmune diseases and other immunopathologies. Aberrations in Treg-mediated immunosuppression are therefore thought to be involved in the development of autoimmune pathologies, but few have been documented. Recent reports indicated a central role for Tregs developing during the neonatal period in the prevention of autoimmune pathology. We therefore investigated the development of Tregs in neonatal NOD mice, an important animal model for autoimmune type 1 diabetes. Surprisingly, we found that, as compared with seven other commonly studied inbred mouse strains, in neonatal NOD mice, exceptionally large proportions of developing Tregs express high levels of GITR and PD-1. The latter phenotype was previously associated with high Treg autoreactivity in C57BL/6 mice, which we here confirm for NOD animals. The proportions of newly developing GITRhighPD-1+ Tregs rapidly drop during the first week of age. A genome-wide genetic screen indicated the involvement of several diabetes susceptibility loci in this trait. Analysis of a congenic mouse strain confirmed that Idd5 contributes to the genetic control of GITRhighPD-1+ Treg development in neonates. Our data thus demonstrate an intriguing and paradoxical correlation between an idiosyncrasy in Treg development in NOD mice and their susceptibility to type 1 diabetes.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1358459/fullthymusregulatory T cellsimmune tolerancetype 1 diabetesIdd5 |
| spellingShingle | Jérémy C. Santamaria Sylvia Vuillier Ariel O. Galindo-Albarrán Sarah Castan Claire Detraves Olivier P. Joffre Paola Romagnoli Joost P. M. van Meerwijk The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse Frontiers in Immunology thymus regulatory T cells immune tolerance type 1 diabetes Idd5 |
| title | The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse |
| title_full | The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse |
| title_fullStr | The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse |
| title_full_unstemmed | The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse |
| title_short | The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse |
| title_sort | type 1 diabetes susceptibility locus idd5 favours robust neonatal development of highly autoreactive regulatory t cells in the nod mouse |
| topic | thymus regulatory T cells immune tolerance type 1 diabetes Idd5 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1358459/full |
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