Survival of mature T cells depends on signaling through HOIP.
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説明
T cell development in the thymus is controlled by a multistep process. The NF-κB pathway regulates T cell development as well as T cell activation at multiple differentiation stages. The linear ubiquitin chain assembly complex (LUBAC) is composed of Sharpin, HOIL-1L and HOIP, and it is crucial for regulating the NF-κB and cell death pathways. However, little is known about the roles of LUBAC in T-cell development and activation. Here, we show that in T-HOIP[Δlinear] mice lacking the ubiquitin ligase activity of LUBAC, thymic CD4[+] or CD8[+] T cell numbers were markedly reduced with severe defects in NKT cell development. HOIP[Δlinear] CD4[+] T cells failed to phosphorylate IκBα and JNK through T cell receptor-mediated stimulation. Mature CD4[+] and CD8[+] T cells in T-HOIP[Δlinear] mice underwent apoptosis more rapidly than control T cells, and it was accompanied by lower CD127 expression on CD4[+]CD24[low] and CD8[+]CD24[low] T cells in the thymus. The enforced expression of CD127 in T-HOIP[Δlinear] thymocytes rescued the development of mature CD8[+] T cells. Collectively, our results showed that LUBAC ligase activity is key for the survival of mature T cells, and suggest multiple roles of the NF-κB and cell death pathways in activating or maintaining T cell-mediated adaptive immune responses.
収録刊行物
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- Scientific reports
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Scientific reports 6 36135-, 2016-10-27
Springer Nature
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詳細情報 詳細情報について
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- CRID
- 1050564285791796352
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- NII論文ID
- 120005867034
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- ISSN
- 20452322
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- HANDLE
- 2433/217250
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- PubMed
- 27786304
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- Crossref
- CiNii Articles
- KAKEN
- OpenAIRE
