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

Kristina Johansson1, John D Gagnon2, Simon K Zhou2

  • 1Department 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.

Cell Reports
|October 20, 2023
PubMed

Insights

MicroRNA 15/16 (miR-15/16) are crucial for regulatory T cells (Tregs) to maintain immune tolerance. Their absence in Tregs leads to inflammation and impaired immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The miR-15/16 family regulates gene networks in T cells, impacting cell cycle, memory, and survival.
  • Downregulation of miR-15/16 upon T cell activation permits effector T cell expansion for sustained responses.

Purpose of the Study:

  • To investigate the immune functions of the miR-15/16 family specifically within regulatory T cells (Tregs).
  • To determine the role of miR-15/16 in maintaining peripheral tolerance and Treg function.

Main Methods:

  • Conditional deletion of miR-15/16 in mouse regulatory T cells.
  • Analysis of Treg protein expression, cell phenotype (FOXP3, CD25, CD127), and function.
  • Assessment of immune activation, multi-organ inflammation, and allergic inflammation in a mouse asthma model.

Main Results:

  • miR-15/16 deficiency impairs Treg function, leading to accumulation of impaired Tregs (FOXP3loCD25loCD127hi).
  • Absence of miR-15/16 causes excessive Treg proliferation, shifting them towards an effector phenotype.
  • Loss of miR-15/16 in Tregs results in spontaneous multi-organ inflammation and exacerbates allergic inflammation.

Conclusions:

  • miR-15/16 expression in Tregs is essential for maintaining peripheral immune tolerance.
  • Dysregulation of miR-15/16 in Tregs compromises immune homeostasis, leading to inflammatory diseases.
Keywords:
CP: ImmunologyT cellT regulatory cellTCF1Tregallergyeffector TregimmunosuppressionmiR-15miR-16miRNA

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