Accumulation of γδ T cells in visceral fat with aging promotes chronic inflammation

Maria E.C. Bruno, Sujata Mukherjee, Whitney L. Powell, Stephanie F. Mori, Franklyn K. Wallace, Beverly K. Balasuriya, Leon C. Su, Arnold J. Stromberg, Donald A. Cohen, Marlene E. Starr

Research output: Contribution to journalArticlepeer-review

Abstract

Adipose tissue dysfunction is strongly linked to the development of chronic inflammation and cardiometabolic disorders in aging. While much attention has been given to the role of resident adipose tissue immune cells in the disruption of homeostasis in obesity, age-specific effects remain understudied. Here, we identified and characterized a population of γδ T cells, which show unique age-dependent accumulation in the visceral adipose tissue (VAT) of both mice and humans. Diet-induced obesity likewise increased γδ T cell numbers; however, the effect was greater in the aged where the increase was independent of fat mass. γδ T cells in VAT express a tissue-resident memory T cell phenotype (CD44hiCD62LlowCD69+) and are predominantly IL-17A-producing cells. Transcriptome analyses of immunomagnetically purified γδ T cells identified significant age-associated differences in expression of genes related to inflammation, immune cell composition, and adipocyte differentiation, suggesting age-dependent qualitative changes in addition to the quantitative increase. Genetic deficiency of γδ T cells in old age improved the metabolic phenotype, characterized by increased respiratory exchange ratio, and lowered levels of IL-6 both systemically and locally in VAT. Decreased IL-6 was predominantly due to reduced production by non-immune stromal cells, primarily preadipocytes, and adipose-derived stem cells. Collectively, these findings suggest that an age-dependent increase of tissue-resident γδ T cells in VAT contributes to local and systemic chronic inflammation and metabolic dysfunction in aging.

Original languageEnglish
Pages (from-to)1761-1778
Number of pages18
JournalGeroScience
Volume44
Issue number3
DOIs
StatePublished - Jun 2022

Bibliographical note

Funding Information:
Research reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103527, the National Center for Research Resources, and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000117, and by NIH grants R01GM129532 and R56AG061508 awarded to MES. Additional support was provided by the Shared Resource Facilities of the University of Kentucky Markey Cancer Center under grant P30CA177558.

Publisher Copyright:
© 2022, The Author(s).

Keywords

  • Adipose tissue
  • Aging
  • Chronic inflammation
  • Gamma delta T cells
  • Obesity

ASJC Scopus subject areas

  • Aging
  • Veterinary (miscellaneous)
  • Complementary and alternative medicine
  • Geriatrics and Gerontology
  • Cardiology and Cardiovascular Medicine

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