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Related Experiment Video

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Analysis of Human Natural Killer Cell Metabolism
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Adipocyte IL-15 regulates local and systemic NK cell development.

Yae-Huei Liou1, Szu-Wen Wang2, Chin-Ling Chang2

  • 1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; and Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.

Journal of Immunology (Baltimore, Md. : 1950)
|July 11, 2014
PubMed
Summary

Adipocytes are a key source of Interleukin-15 (IL-15), crucial for Natural Killer (NK) cell development. This study reveals adipose tissue as a novel niche supporting systemic NK cell production.

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Expansion and Adipogenesis Induction of Adipocyte Progenitors from Perivascular Adipose Tissue Isolated by Magnetic Activated Cell Sorting
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Area of Science:

  • Immunology
  • Cell Biology
  • Endocrinology

Background:

  • Natural Killer (NK) cell development and homeostasis depend on Interleukin-15 (IL-15).
  • While hematopoietic sources of IL-15 are known, parenchymal sources remain largely unidentified.
  • The specific contribution of non-hematopoietic cells to IL-15 production for NK cell development is unclear.

Purpose of the Study:

  • To identify parenchymal cell sources of IL-15 essential for NK cell development.
  • To investigate the role of adipocytes as a potential source of IL-15.
  • To elucidate the contribution of adipose tissue-derived IL-15 to systemic NK cell homeostasis.

Main Methods:

  • Generation and analysis of two distinct lines of adipocyte-specific Interleukin-15 knockout (Il15(-/-)) mice.
  • Assessment of IL-15 production in adipose tissue.
  • Evaluation of NK cell development and populations in spleen, liver, and adipose tissue.
  • Analysis of NK cell progenitor presence in adipose tissue niches.
  • Challenging recipient mice with NK cells derived from transplanted adipose tissue.

Main Results:

  • Adipocytes were identified as a significant parenchymal source of IL-15, supporting NK cell development nonredundantly.
  • Adipocyte-specific Il15(-/-) mice exhibited reduced IL-15 in adipose tissue and impaired NK cell development systemically (spleen, liver, adipose tissue).
  • Adipose tissue was confirmed to harbor NK cell progenitors, functioning as a developmental niche.
  • NK cells originating from transplanted adipose tissue successfully repopulated the spleen and liver of recipient mice.

Conclusions:

  • Adipocytes represent a critical parenchymal source of IL-15, vital for NK cell development.
  • Adipose tissue serves as an important niche for NK cell development, contributing to the systemic pool of NK cells.
  • Adipocyte-derived IL-15 plays a key role in maintaining NK cell homeostasis across multiple organs.