Grants and Contracts Details
Description
Abstract
Detailed description of model system used for the proposed research: C57BL/6 mice,
transgenic mouse strains (TCRδ and IL-17A KO), primary mouse cells, cell lines (human and
mouse)
Adipose tissue dysfunction is linked to metabolic derangements and chronic low-grade systemic
inflammation, which are characteristic of the aging process and underlie numerous age-related
pathologies. This proposal is centered on our novel findings that visceral adipose tissue (VAT) of
aged mice contains nearly 10-fold more gamma delta (γδ) T cells than young-adult mice and that
aged mice lacking γδ T cells have reduced systemic and VAT inflammation, and an improved
metabolic phenotype. Our central hypothesis is that accumulation of γδ T cells in VAT promotes
age-associated adipose tissue dysfunction. The manner with which these cells come to
accumulate in VAT with age, and the mechanisms for their action specifically in VAT are not
known. Specific Aim 1 will characterize the VAT γδ T cell pool and delineate age-dependent
differences. Specific Aim 2 will establish that γδ T cells are drivers of preadipocyte senescence,
which contributes to chronic adipose tissue inflammation in old age. Specific Aim 3 will define a
role for γδ T cells in age-related metabolic dysfunction through PPARγ suppression. These
studies will utilize aged mice genetically deficient in γδ T cells and mice that lack the cytokine IL-
17A, as well as various in vivo, ex vivo, and in vitro approaches. Collectively, this project will
establish the novel concept that VAT-resident γδ T cells are drivers of chronic inflammation and
adipose tissue dysfunction in the aged, and will elucidate mechanisms underlying these
processes. As aging poses the greatest risk for the development of chronic conditions, the
generated data will aid in the identification of strategies to reduce the burden of a long list of age-
related disorders, for which chronic inflammation is a common denominator.
Status | Active |
---|---|
Effective start/end date | 12/31/22 → 12/31/25 |
Funding
- American Federation for Aging Research: $373,000.00
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