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Title: Survival of mature T cells depends on signaling through HOIP.
Authors: Okamura, Kazumi
Kitamura, Akiko
Sasaki, Yoshiteru  kyouindb  KAKEN_id
Chung, Doo Hyun
Kagami, Shoji
Iwai, Kazuhiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Yasutomo, Koji
Author's alias: 佐々木, 義輝
岩井, 一宏
Issue Date: 27-Oct-2016
Publisher: Springer Nature
Journal title: Scientific reports
Volume: 6
Thesis number: 36135
Abstract: 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.
Rights: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
DOI(Published Version): 10.1038/srep36135
PubMed ID: 27786304
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