論文

査読有り 国際誌
2021年8月

PD-L1 on mast cells suppresses effector CD8+ T-cell activation in the skin in murine contact hypersensitivity

Journal of Allergy and Clinical Immunology
  • Tomoko Hirano
  • Tetsuya Honda
  • Shuto Kanameishi
  • Yuki Honda
  • Gyohei Egawa
  • Akihiko Kitoh
  • Saeko Nakajima
  • Atsushi Otsuka
  • Takashi Nomura
  • Teruki Dainichi
  • Tomonori Yaguchi
  • Takashi Inozume
  • Tatsuki R. Kataoka
  • Koji Tamada
  • Kenji Kabashima
  • 全て表示

148
2
開始ページ
563
終了ページ
573.e7
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jaci.2020.12.654
出版者・発行元
Elsevier BV

BACKGROUND: The programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is known to inhibit the activation of effector CD8+ T cells. However, just how this regulatory pathway is involved in the pathophysiology of CD8+ T-cell-mediated inflammatory skin diseases remains unclear. OBJECTIVE: Our aim was to elucidate the mechanisms by which the PD-1/PD-L1 pathway exerts its regulatory roles in CD8+ T-cell-mediated cutaneous immune responses. METHODS: PD-L1-deficient (Pdl1-/-) mice were used for the murine contact hypersensitivity model. Inflammatory responses such as IFN-γ production from CD8+ T cells in the skin was evaluated by flow cytometry. RESULTS: Compared with wild-type mice, Pdl1-/- mice exhibited exacerbated ear swelling and increased numbers of IFN-γ+ CD8+ T cells in the skin. Adoptive T-cell transfer experiments revealed the involvement of the PD-1/PD-L1 pathway in the elicitation phase of contact hypersensitivity. Bone marrow chimera experiments showed that PD-L1 on radioresistant cells was responsible for this regulatory pathway. Flow cytometric analysis revealed that among the radioresistant cells in the skin, PD-L1 was most highly expressed on mast cells (MCs) before and after elicitation. Administration of anti-PD-L1 blocking antibody during the elicitation phase significantly enhanced ear swelling responses and increased the number of IFN-γ+CD8+ T cells in the skin of wild-type mice, whereas no significant effects were observed in MC-deficient (WBB6F1/J-KitW/KitW-v/J and C57BL/6-KitW-sh/W-sh) mice. The high level of expression of PD-L1 on human skin MCs was confirmed by database analysis and immunohistochemical analysis. CONCLUSION: PD-L1 on MCs negatively regulates CD8+ T-cell activation in the skin.

リンク情報
DOI
https://doi.org/10.1016/j.jaci.2020.12.654
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33581199
ID情報
  • DOI : 10.1016/j.jaci.2020.12.654
  • ISSN : 0091-6749
  • PubMed ID : 33581199

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