Obesity accelerates T cell senescence in murine visceral adipose tissue.
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 CD44hiCD62LloCD4+ 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-1-resistant manner in vitro. The features of CD153+PD-1+CD44hiCD4+ T cells were highly reminiscent of senescence-associated CD4+ T cells that normally increase with age. Adoptive transfer of CD153+PD-1+CD44hiCD4+ 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+PD-1+CD44hiCD4+ 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.
Kohsuke
K
Shirakawa
Xiaoxiang
X
Yan
Ken
K
Shinmura
Jin
J
Endo
Masaharu
M
Kataoka
Yoshinori
Y
Katsumata
Tsunehisa
T
Yamamoto
Atsushi
A
Anzai
Sarasa
S
Isobe
Naohiro
N
Yoshida
Hiroshi
H
Itoh
Ichiro
I
Manabe
Miho
M
Sekai
Yoko
Y
Hamazaki
Keiichi
K
Fukuda
Nagahiro
N
Minato
Motoaki
M
Sano
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D053495:Osteopontin / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D004041:Dietary Fats; D011948:Receptors, Antigen, T-Cell; C506896:Spp1 protein, mouse; D053495:Osteopontin