2021年12月7日
Peripheral tolerance by Treg via constraining OX40 signal in autoreactive T cells against desmoglein 3, a target antigen in pemphigus
Proceedings of the National Academy of Sciences
- 巻
- 118
- 号
- 49
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1073/pnas.2026763118
- 出版者・発行元
- Proceedings of the National Academy of Sciences
Significance
Immune tolerance is crucial to prevent harmful immune reactions against self-antigens and well operated by central thymic tolerance and peripheral tissue tolerance. However, peripheral tolerance had been investigated under influence from thymic tolerance. We successfully decoupled peripheral tolerance from thymic tolerance by utilizing autoantigen-deficient thymus. Experiments revealed that self-antigen presentation in steady state initiated proliferation but subsequent disappearance of autoreactive CD4 + T cells in draining lymph nodes. After screening of representative candidates, including Ctla4, autoimmune regulator, and Pd-1, the mechanism was found to depend on regulatory T cell (Treg) function that constrained OX40 signaling of the T cells. This study presented fundamental, but potent, Treg-mediated tolerance mechanisms of peripheral tissues to prevent autoimmunity as compensatory roles for central tolerance.
Immune tolerance is crucial to prevent harmful immune reactions against self-antigens and well operated by central thymic tolerance and peripheral tissue tolerance. However, peripheral tolerance had been investigated under influence from thymic tolerance. We successfully decoupled peripheral tolerance from thymic tolerance by utilizing autoantigen-deficient thymus. Experiments revealed that self-antigen presentation in steady state initiated proliferation but subsequent disappearance of autoreactive CD4 + T cells in draining lymph nodes. After screening of representative candidates, including Ctla4, autoimmune regulator, and Pd-1, the mechanism was found to depend on regulatory T cell (Treg) function that constrained OX40 signaling of the T cells. This study presented fundamental, but potent, Treg-mediated tolerance mechanisms of peripheral tissues to prevent autoimmunity as compensatory roles for central tolerance.
- リンク情報
- ID情報
-
- DOI : 10.1073/pnas.2026763118
- ISSN : 0027-8424
- eISSN : 1091-6490
- PubMed ID : 34848535
- PubMed Central 記事ID : PMC8670434