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

Author

Listed:
  • Shota Yoshida

    (Osaka University Graduate School of Medicine
    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
    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)

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.

Suggested Citation

  • Shota Yoshida & Hironori Nakagami & Hiroki Hayashi & Yuka Ikeda & Jiao Sun & Akiko Tenma & Hideki Tomioka & Tomohiro Kawano & Munehisa Shimamura & Ryuichi Morishita & Hiromi Rakugi, 2020. "The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16347-w
    DOI: 10.1038/s41467-020-16347-w
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