The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice.
Shota YoshidaHironori NakagamiHiroki HayashiYuka IkedaJiao SunAkiko TenmaHideki TomiokaTomohiro KawanoMunehisa ShimamuraRyuichi MorishitaHiromi RakugiPublished in: Nature communications (2020)
Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells, defined as CD4+ CD44high CD62Llow PD-1+ CD153+ cells, accumulate in visceral adipose tissues (VAT) in obese individuals. Here, we show the long-lasting effect of using CD153 vaccination to remove senescent T cells from high-fat diet (HFD)-induced obese C57BL/6J mice. We administered a CD153 peptide-KLH (keyhole limpet hemocyanin) conjugate vaccine with Alhydrogel (CD153-Alum) or CpG oligodeoxynucleotide (ODN) 1585 (CD153-CpG) and confirmed an increase in anti-CD153 antibody levels that was sustained for several months. After being fed a HFD for 10-11 weeks, adipose senescent T cell accumulation was significantly reduced in the VAT of CD153-CpG-vaccinated mice, accompanied by glucose tolerance and insulin resistance. A complement-dependent cytotoxicity (CDC) assay indicated that the mouse IgG2 antibody produced in the CD153-CpG-vaccinated mice successfully reduced the number of senescent T cells. The CD153-CpG vaccine is an optional tool for senolytic therapy.
Keyphrases
- high fat diet
- insulin resistance
- adipose tissue
- dna methylation
- nk cells
- type diabetes
- high fat diet induced
- induced apoptosis
- stem cells
- gene expression
- drug delivery
- cell proliferation
- mesenchymal stem cells
- bone marrow
- high throughput
- weight loss
- signaling pathway
- cell death
- cell therapy
- single cell
- high glucose
- endoplasmic reticulum stress
- drug induced
- diabetic rats