No abstract

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.

A n acute aortic dissection (AAD) is initiated by an intimal tear, with resultant propagation within the middle third of the medial layer of the aorta. 1 To delineate treatment, the Stanford classification divides AAD into 2 types, type A and type B. Type A affects the ascending aorta, whereas type B does not. Type A AAD is more severe because of the higher mortality rate of 20% by 24 hours, 30% by 48 hours, 40% at 1 week, and 50% at 1 month.2 Thus, surgical repair is the first choice of treatment for patients with type A AAD to prevent life-threatening complications, including aortic rupture and cardiac tamponade. Although type B AAD is generally more benign and medical treatment for high blood pressure and intolerant pain can improve the patient's clinical outcome, a substantial proportion of medically treated patients still encounter catastrophic events within 7 days, such as aortic expansion and subsequent aortic rupture, visceral ischemia, and lung oxygenation impairment.2,3 Thoracic endovascular repair with stent grafting is the emerging therapeutic strategy Methods and Results:

OPN is almost exclusively produced by galectin-3CD206 macrophages, which specifically appear in the infarct myocardium after MI. The IL-10-STAT3-galectin-3 axis is essential for OPN-producing reparative macrophage polarization after myocardial infarction, and these macrophages contribute to tissue repair by promoting fibrosis and clearance of apoptotic cells. These results suggest that galectin-3 may contribute to reparative fibrosis in the infarct myocardium by controlling OPN levels.