An essential role for miR-15/16 in Treg suppression and restriction of proliferation

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

Cell Reports (Oct 2023)

An essential role for miR-15/16 in Treg suppression and restriction of proliferation

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

Affiliations

Kristina Johansson: Department 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, Sweden
John D. Gagnon: Department 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
Simon K. Zhou: Department 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
Marlys S. Fassett: Department 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, USA
Andrew W. Schroeder: Department of Medicine, Genomics CoLab, University of California, San Francisco, San Francisco, CA 94143, USA
Robin Kageyama: Department 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
Rodriel A. Bautista: 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
Hewlett Pham: Department 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
Prescott G. Woodruff: 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
K. Mark Ansel: Department 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 author

Journal volume & issue: Vol. 42, no. 10
p. 113298

Abstract

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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.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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