An essential role for miR-15/16 in Treg suppression and restriction of proliferation
Summary: The miR-15/16 family targets a large network of genes in T cells to restrict their cell cycle, memory formation, and survival. Upon T cell activation, miR-15/16 are downregulated, allowing rapid expansion of differentiated effector T cells to mediate a sustained response. Here, we used cond...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-10-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723013104 |
| _version_ | 1797655110999867392 |
|---|---|
| author | Kristina Johansson John D. Gagnon Simon K. Zhou Marlys S. Fassett Andrew W. Schroeder Robin Kageyama Rodriel A. Bautista Hewlett Pham Prescott G. Woodruff K. Mark Ansel |
| author_facet | Kristina Johansson John D. Gagnon Simon K. Zhou Marlys S. Fassett Andrew W. Schroeder Robin Kageyama Rodriel A. Bautista Hewlett Pham Prescott G. Woodruff K. Mark Ansel |
| author_sort | Kristina Johansson |
| collection | DOAJ |
| description | Summary: The miR-15/16 family targets a large network of genes in T cells to restrict their cell cycle, memory formation, and survival. Upon T cell activation, miR-15/16 are downregulated, allowing rapid expansion of differentiated effector T cells to mediate a sustained response. Here, we used conditional deletion of miR-15/16 in regulatory T cells (Tregs) to identify immune functions of the miR-15/16 family in T cells. miR-15/16 are indispensable to maintain peripheral tolerance by securing efficient suppression by a limited number of Tregs. miR-15/16 deficiency alters expression of critical Treg proteins and results in accumulation of functionally impaired FOXP3loCD25loCD127hi Tregs. Excessive proliferation in the absence of miR-15/16 shifts Treg fate and produces an effector Treg phenotype. These Tregs fail to control immune activation, leading to spontaneous multi-organ inflammation and increased allergic inflammation in a mouse model of asthma. Together, our results demonstrate that miR-15/16 expression in Tregs is essential to maintain immune tolerance. |
| first_indexed | 2024-03-11T17:09:25Z |
| format | Article |
| id | doaj.art-769f6088e5054e208c6c0b1f112161c5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-11T17:09:25Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-769f6088e5054e208c6c0b1f112161c52023-10-20T06:39:30ZengElsevierCell Reports2211-12472023-10-014210113298An essential role for miR-15/16 in Treg suppression and restriction of proliferationKristina Johansson0John D. Gagnon1Simon K. Zhou2Marlys S. Fassett3Andrew W. Schroeder4Robin Kageyama5Rodriel A. Bautista6Hewlett Pham7Prescott G. Woodruff8K. Mark Ansel9Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, 40530 Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, 40530 Gothenburg, SwedenDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Medicine, Genomics CoLab, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USASandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USASandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA; Corresponding authorSummary: The miR-15/16 family targets a large network of genes in T cells to restrict their cell cycle, memory formation, and survival. Upon T cell activation, miR-15/16 are downregulated, allowing rapid expansion of differentiated effector T cells to mediate a sustained response. Here, we used conditional deletion of miR-15/16 in regulatory T cells (Tregs) to identify immune functions of the miR-15/16 family in T cells. miR-15/16 are indispensable to maintain peripheral tolerance by securing efficient suppression by a limited number of Tregs. miR-15/16 deficiency alters expression of critical Treg proteins and results in accumulation of functionally impaired FOXP3loCD25loCD127hi Tregs. Excessive proliferation in the absence of miR-15/16 shifts Treg fate and produces an effector Treg phenotype. These Tregs fail to control immune activation, leading to spontaneous multi-organ inflammation and increased allergic inflammation in a mouse model of asthma. Together, our results demonstrate that miR-15/16 expression in Tregs is essential to maintain immune tolerance.http://www.sciencedirect.com/science/article/pii/S2211124723013104CP: Immunology |
| spellingShingle | Kristina Johansson John D. Gagnon Simon K. Zhou Marlys S. Fassett Andrew W. Schroeder Robin Kageyama Rodriel A. Bautista Hewlett Pham Prescott G. Woodruff K. Mark Ansel An essential role for miR-15/16 in Treg suppression and restriction of proliferation Cell Reports CP: Immunology |
| title | An essential role for miR-15/16 in Treg suppression and restriction of proliferation |
| title_full | An essential role for miR-15/16 in Treg suppression and restriction of proliferation |
| title_fullStr | An essential role for miR-15/16 in Treg suppression and restriction of proliferation |
| title_full_unstemmed | An essential role for miR-15/16 in Treg suppression and restriction of proliferation |
| title_short | An essential role for miR-15/16 in Treg suppression and restriction of proliferation |
| title_sort | essential role for mir 15 16 in treg suppression and restriction of proliferation |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723013104 |
| work_keys_str_mv | AT kristinajohansson anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT johndgagnon anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT simonkzhou anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT marlyssfassett anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT andrewwschroeder anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT robinkageyama anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT rodrielabautista anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT hewlettpham anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT prescottgwoodruff anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT kmarkansel anessentialroleformir1516intregsuppressionandrestrictionofproliferation AT kristinajohansson essentialroleformir1516intregsuppressionandrestrictionofproliferation AT johndgagnon essentialroleformir1516intregsuppressionandrestrictionofproliferation AT simonkzhou essentialroleformir1516intregsuppressionandrestrictionofproliferation AT marlyssfassett essentialroleformir1516intregsuppressionandrestrictionofproliferation AT andrewwschroeder essentialroleformir1516intregsuppressionandrestrictionofproliferation AT robinkageyama essentialroleformir1516intregsuppressionandrestrictionofproliferation AT rodrielabautista essentialroleformir1516intregsuppressionandrestrictionofproliferation AT hewlettpham essentialroleformir1516intregsuppressionandrestrictionofproliferation AT prescottgwoodruff essentialroleformir1516intregsuppressionandrestrictionofproliferation AT kmarkansel essentialroleformir1516intregsuppressionandrestrictionofproliferation |