title: Survival of mature T cells depends on signaling through HOIP.
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-HOIPΔlinearmice lacking the ubiquitin ligase activity of LUBAC, thymic CD4+or CD8+T cell numbers were markedly reduced with severe defects in NKT cell development. HOIPΔlinearCD4+T cells failed to phosphorylate IκBα and JNK through T cell receptor-mediated stimulation. Mature CD4+and CD8+T cells in T-HOIPΔlinearmice underwent apoptosis more rapidly than control T cells, and it was accompanied by lower CD127 expression on CD4+CD24lowand CD8+CD24lowT cells in the thymus. The enforced expression of CD127 in T-HOIPΔlinearthymocytes 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.
authors: Department of Immunology &Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.|Department of Pediatrics, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors: Kazumi
authors: K
authors: Okamura
authors: Department of Immunology &Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors: Akiko
authors: A
authors: Kitamura
authors: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Yoshiteru
authors: Y
authors: Sasaki
authors: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors: Doo Hyun
authors: DH
authors: Chung
authors: Department of Pediatrics, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors: Shoji
authors: S
authors: Kagami
authors: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Kazuhiro
authors: K
authors: Iwai
authors: Department of Immunology &Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, Japan.
authors: Koji
authors: K
authors: Yasutomo
mesh_terms: D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002470:Cell Survival; D007371:Interferon-gamma / Q000097:blood; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D053699:Interleukin-7 Receptor alpha Subunit; D046912:Multiprotein Complexes; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; C492590:Rnf31 protein, mouse; D044767:Ubiquitin-Protein Ligases; D048031:JNK Mitogen-Activated Protein Kinases