RAG suppresses group 2 innate lymphoid cells
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| Publicado en: | eLife vol. 13 (2025) |
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| Autor principal: | |
| Otros Autores: | , , , , , , , , , , , |
| Publicado: |
eLife Sciences Publications Ltd.
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| Acceso en línea: | Citation/Abstract Full Text + Graphics Full Text - PDF |
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| 001 | 3204558862 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 2050-084X | ||
| 024 | 7 | |a 10.7554/eLife.98287 |2 doi | |
| 035 | |a 3204558862 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 100 | 1 | |a Ver Heul Aaron M |u https://ror.org/036c27j91 Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine St. Louis United States | |
| 245 | 1 | |a RAG suppresses group 2 innate lymphoid cells | |
| 260 | |b eLife Sciences Publications Ltd. |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Antigen specificity is the central trait distinguishing adaptive from innate immune function. Assembly of antigen-specific T cell and B cell receptors occurs through V(D)J recombination mediated by the Recombinase Activating Gene endonucleases RAG1 and RAG2 (collectively called RAG). In the absence of RAG, mature T and B cells do not develop and thus RAG is critically associated with adaptive immune function. In addition to adaptive T helper 2 (Th2) cells, group 2 innate lymphoid cells (ILC2s) contribute to type 2 immune responses by producing cytokines like Interleukin-5 (IL-5) and IL-13. Although it has been reported that RAG expression modulates the function of innate natural killer (NK) cells, whether other innate immune cells such as ILC2s are affected by RAG remains unclear. We find that in RAG-deficient mice, ILC2 populations expand and produce increased IL-5 and IL-13 at steady state and contribute to increased inflammation in atopic dermatitis (AD)-like disease. Furthermore, we show that RAG modulates ILC2 function in a cell-intrinsic manner independent of the absence or presence of adaptive T and B lymphocytes. Lastly, employing multiomic single cell analyses of RAG1 lineage-traced cells, we identify key transcriptional and epigenomic ILC2 functional programs that are suppressed by a history of RAG expression. Collectively, our data reveal a novel role for RAG in modulating innate type 2 immunity through suppression of ILC2s. | |
| 653 | |a T cell receptors | ||
| 653 | |a Immunity (Disease) | ||
| 653 | |a V(D)J recombination | ||
| 653 | |a RAG2 protein | ||
| 653 | |a Disease | ||
| 653 | |a Lymphocytes T | ||
| 653 | |a Lymphatic system | ||
| 653 | |a RAG1 protein | ||
| 653 | |a Atopic dermatitis | ||
| 653 | |a Cytokines | ||
| 653 | |a Natural killer cells | ||
| 653 | |a Lymphocytes | ||
| 653 | |a Recombinase | ||
| 653 | |a Lymphoid cells | ||
| 653 | |a Receptor mechanisms | ||
| 653 | |a Inflammation | ||
| 653 | |a Antigens | ||
| 653 | |a Pathogenesis | ||
| 653 | |a Lymphocytes B | ||
| 653 | |a Interleukin 5 | ||
| 653 | |a Interleukin 13 | ||
| 700 | 1 | |a Mack, Madison |u Immunology and Inflammation Research Therapeutic Area, Sanofi Cambridge United States | |
| 700 | 1 | |a Zamidar Lydia |u https://ror.org/04a9tmd77 Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai New York United States | |
| 700 | 1 | |a Tamari Masato |u https://ror.org/04a9tmd77 Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai New York United States | |
| 700 | 1 | |a Ting-Lin, Yang |u https://ror.org/036c27j91 Division of Dermatology, Department of Medicine, Washington University School of Medicine St. Louis United States | |
| 700 | 1 | |a Trier, Anna M |u https://ror.org/036c27j91 Division of Dermatology, Department of Medicine, Washington University School of Medicine St. Louis United States | |
| 700 | 1 | |a Do-Hyun, Kim |u https://ror.org/036c27j91 Department of Pathology and Immunology, Washington University School of Medicine St. Louis United States | |
| 700 | 1 | |a Janzen-Meza, Hannah |u https://ror.org/036c27j91 Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine St. Louis United States | |
| 700 | 1 | |a Van Dyken Steven J |u https://ror.org/036c27j91 Department of Pathology and Immunology, Washington University School of Medicine St. Louis United States | |
| 700 | 1 | |a Chyi-Song, Hsieh |u https://ror.org/036c27j91 Division of Rheumatology, Department of Medicine, Washington University School of Medicine St. Louis United States | |
| 700 | 1 | |a Karo, Jenny M |u https://ror.org/02r109517 Immunology and Microbial Pathogenesis Program, Graduate School of Medical Sciences, Weill Cornell Medical College New York United States | |
| 700 | 1 | |a Sun, Joseph C |u https://ror.org/02r109517 Immunology and Microbial Pathogenesis Program, Graduate School of Medical Sciences, Weill Cornell Medical College New York United States | |
| 700 | 1 | |a Kim, Brian S |u https://ror.org/04a9tmd77 Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai New York United States | |
| 773 | 0 | |t eLife |g vol. 13 (2025) | |
| 786 | 0 | |d ProQuest |t Science Database | |
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