The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice

Shota Yoshida, Hironori Nakagami (), Hiroki Hayashi, Yuka Ikeda, Jiao Sun, Akiko Tenma, Hideki Tomioka, Tomohiro Kawano, Munehisa Shimamura, Ryuichi Morishita and Hiromi Rakugi
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Shota Yoshida: Osaka University Graduate School of Medicine
Hironori Nakagami: Osaka University Graduate School of Medicine
Hiroki Hayashi: Osaka University Graduate School of Medicine
Yuka Ikeda: FunPep Co., Ltd.
Jiao Sun: Osaka University Graduate School of Medicine
Akiko Tenma: FunPep Co., Ltd.
Hideki Tomioka: FunPep Co., Ltd.
Tomohiro Kawano: Osaka University Graduate School of Medicine
Munehisa Shimamura: Osaka University Graduate School of Medicine
Ryuichi Morishita: Osaka University Graduate School of Medicine
Hiromi Rakugi: Osaka University Graduate School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-16347-w

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