Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 126, Issue 12, Pages 4626-4639Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI88606
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Funding
- Japan Society for the Promotion of Science KAKENHI [22590814]
- Japan Foundation for Aging and Health
- Takeda Medical Research Foundation
- 3rdAnnual Research Award Grant of Japanese Anti-Aging Medicine
- Vehicle Racing Commemorative Foundation
- JST PREST
- JSPS KAKENHI [15H04825, 15H01160]
- Grants-in-Aid for Scientific Research [22590814, 15H01160, 24111008, 15H04825, 15K19125, 24111001] Funding Source: KAKEN
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Chronic inflammation in visceral adipose tissue (VAT) precipitates the development of cardiometabolic disorders. Although changes in T cell function associated with visceral obesity are thought to affect chronic VAT inflammation, the specific features of these changes remain elusive. Here, we have determined that a high-fat diet (HFD) caused a preferential increase and accumulation of CD44(hi)CD62L(lo)CD4(+) T cells that constitutively express PD-1 and CD153 in a B cell-dependent manner in VAT. These cells possessed characteristics of cellular senescence and showed a strong activation of Spp1 (encoding osteopontin [OPN]) in VAT. Upon T cell receptor stimulation, these T cells also produced large amounts of OPN in a PD-1resistant manner in vitro. The features of CD153(+)PD-1(+)CD44(hi)CD4(+) T cells were highly reminiscent of senescence-associated CD4(+) T cells that normally increase with age. Adoptive transfer of CD153(+)PD-1(+)CD44(hi)CD4(+) T cells from HFD-fed WT, but not Spp1-deficient, mice into the VAT of lean mice fed a normal diet recapitulated the essential features of VAT inflammation and insulin resistance. Our results demonstrate that a distinct CD153(+)PD1(+)CD44(hi)CD4(+) T cell population that accumulates in the VAT of HFD-fed obese mice causes VAT inflammation by producing large amounts of OPN. This finding suggests a link between visceral adiposity and immune aging.
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