Insulin Receptor–Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice
| العنوان: | Insulin Receptor–Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice |
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| المؤلفون: | Mark A. Atkinson, Tasneem Al-Huniti, Nirdesh K Gupta, Tian Chen, Jamie L. Felton, James D Horner, Steven K. Lundy, Michael P. Morran, Douglas Rogers, Emily Esakov, Swapnaa Balaji, Andrea Nestor Kalinoski, Neha Nandedkar-Kulkarni, Brigid Gregg, Kanakadurga Singer, Marcia F. McInerney, James D. Bretz |
| المصدر: | J Immunol |
| بيانات النشر: | The American Association of Immunologists, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, Risk, Genetically modified mouse, medicine.medical_specialty, Adolescent, endocrine system diseases, T-Lymphocytes, T cell, medicine.medical_treatment, Immunology, Mice, Transgenic, Article, Mice, Young Adult, Cell Movement, Mice, Inbred NOD, Insulin-Secreting Cells, Internal medicine, medicine, Animals, Humans, Immunology and Allergy, Child, Pancreas, NOD mice, Type 1 diabetes, biology, Chemistry, Insulin, medicine.disease, Receptor, Insulin, Mice, Inbred C57BL, Disease Models, Animal, Insulin receptor, Diabetes Mellitus, Type 1, medicine.anatomical_structure, Endocrinology, biology.protein, Female, Insulitis |
| الوصف: | Insulin receptor (IR) expression on the T cell surface can indicate an activated state; however, the IR is also chemotactic, enabling T cells with high IR expression to physically move toward insulin. In humans with type 1 diabetes (T1D) and the NOD mouse model, a T cell–mediated autoimmune destruction of insulin-producing pancreatic β cells occurs. In previous work, when purified IR+ and IR− T cells were sorted from diabetic NOD mice and transferred into irradiated nondiabetic NOD mice, only those that received IR+ T cells developed insulitis and diabetes. In this study, peripheral blood samples from individuals with T1D (new onset to 14 y of duration), relatives at high-risk for T1D, defined by positivity for islet autoantibodies, and healthy controls were examined for frequency of IR+ T cells. High-risk individuals had significantly higher numbers of IR+ T cells as compared with those with T1D (p < 0.01) and controls (p < 0.001); however, the percentage of IR+ T cells in circulation did not differ significantly between T1D and control subjects. With the hypothesis that IR+ T cells traffic to the pancreas in T1D, we developed a (to our knowledge) novel mouse model exhibiting a FLAG-tagged mouse IR on T cells on the C57BL/6 background, which is not susceptible to developing T1D. Interestingly, these C57BL/6-CD3FLAGmIR/mfm mice showed evidence of increased IR+ T cell trafficking into the islets compared with C57BL/6 controls (p < 0.001). This transgenic animal model provides a (to our knowledge) novel platform for investigating the influence of IR expression on T cell trafficking and the development of insulitis. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d0b0469b6fd27c7f018eab522859d75Test https://doi.org/10.4049/jimmunol.1900357Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6d0b0469b6fd27c7f018eab522859d75 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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