Cutting Edge: Origins, Recruitment, and Regulation of CD11c+ Cells in Inflamed Islets of Autoimmune Diabetes Mice
| Autor: | Ashley Mahne, Allyson Spence, Qizhi Tang, Ansuman T. Satpathy, Vinh Son Nguyen, Kenneth M. Murphy, Joanna E. Klementowicz |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system Chemokine endocrine system diseases T-Lymphocytes 1.1 Normal biological development and functioning Immunology CD11c Inflammation Autoimmunity Biology CCL8 Autoimmune Disease CCL5 Monocytes 03 medical and health sciences Islets of Langerhans Mice Cell Movement Underpinning research medicine Diabetes Mellitus Immunology and Allergy Animals Chemokine CCL8 Chemokine CCL5 Metabolic and endocrine NOD mice geography geography.geographical_feature_category Monocyte Diabetes hemic and immune systems Dendritic Cells Islet Regulatory Cell biology CD11c Antigen 030104 developmental biology medicine.anatomical_structure biology.protein Inbred NOD Female medicine.symptom Type 1 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950), vol 199, iss 1 |
| Popis: | In NOD mice, CD11c+ cells increase greatly with islet inflammation and contribute to autoimmune destruction of pancreatic β cells. In this study, we investigated their origin and mechanism of recruitment. CD11c+ cells in inflamed islets resembled classical dendritic cells based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent dendritic-cell lineage. Instead, monocyte precursors could give rise to CD11c+ cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c+ cells was partially dependent on their receptor Ccr5. Treatment with islet Ag-specific regulatory T cells led to a marked decrease of Ccl5 and Ccl8, and a reduction of monocyte recruitment. These results implicate a monocytic origin of CD11c+ cells in inflamed islets and suggest that therapeutic regulatory T cells directly or indirectly regulate their influx by altering the chemotactic milieu in the islets. |
| Databáze: | OpenAIRE |
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