論文

査読有り 国際誌
2019年10月

Silencing of PD-L2/B7-DC by Topical Application of Small Interfering RNA Inhibits Elicitation of Contact Hypersensitivity.

The Journal of investigative dermatology
  • Emi Furusawa
  • ,
  • Tatsukuni Ohno
  • ,
  • Shigenori Nagai
  • ,
  • Taisei Noda
  • ,
  • Takuya Komiyama
  • ,
  • Katsunori Kobayashi
  • ,
  • Hidetoshi Hamamoto
  • ,
  • Michiyo Miyashin
  • ,
  • Hiroo Yokozeki
  • ,
  • Miyuki Azuma

139
10
開始ページ
2164
終了ページ
2173
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jid.2019.02.037

PD-L2 is a ligand for the immune checkpoint receptor PD-1; however, its regulatory function is unclear. We previously reported that silencing of CD86 in cutaneous dendritic cells by topical application of small interfering RNA (siRNA) inhibits the elicitation of contact hypersensitivity (CHS). Here, we investigated the effects of topical application of PD-L2 siRNA on allergic skin disease. PD-L2 was induced in dendritic cells concurrently with the elevation of major histocompatibility complex class II and CD86 expression. Topical application of PD-L2 siRNA inhibited the elicitation of CHS by suppressing early proinflammatory cytokine expression and migration of hapten-carrying dendritic cells into lymph nodes. Local injection of neutralizing anti-PD-L2 mAb inhibited CHS to the same extent. PD-L2 siRNA treatment inhibited CHS in PD-1/PD-L1 double knockout mice and in the sensitized T-cell-transferred skin. These results suggest that the effects of PD-L2 silencing are independent of PD-1 but dependent on local memory T cells. Most of the inhibitory effects of PD-L2 and CD86 silencing on CHS were comparable, but PD-L2 siRNA treatment did not inhibit atopic disease-like manifestations and T helper type 2 responses in NC/Nga mice. Our results suggest that PD-L2 in cutaneous dendritic cells acts as a costimulator rather than a regulator. Local PD-L2 silencing by topical application of siRNA represents a therapeutic approach for contact allergy.

リンク情報
DOI
https://doi.org/10.1016/j.jid.2019.02.037
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30978356

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