title: Menin Plays a Critical Role in the Regulation of the Antigen-Specific CD8+ T Cell Response upon Listeria Infection.
abstract: Menin, a tumor suppressor protein, is encoded by the MEN1 gene in humans. Certain germinal mutations of MEN1 induce an autosomal-dominant syndrome that is characterized by concurrent parathyroid adenomas and several other tumor types. Although menin is also expressed in hematopoietic lineages, its role in CD8+T cells remains unclear. We generated Meninflox/floxCD4-Cre (Menin-KO) mice by crossing Meninflox/floxmice with CD4-Cre transgenic (Tg) mice to determine the role of menin in CD8+T cells. Wild-type (WT) and Menin-KO mice were infected with Listeria monocytogenes expressing OVA to analyze the immune response of Ag-specific CD8+T cells. Menin deficiency resulted in an impaired primary immune response by CD8+T cells. On day 7, there were fewer Menin-KO OVA-specific CD8+T cells compared with WT cells. Next, we adoptively transferred WT and Menin-KO OT-1 Tg CD8+T cells into congenic recipient mice and infected them with L. monocytogenes expressing OVA to determine the CD8+T cell-intrinsic effect. Menin-KO OT-1 Tg CD8+T cells were outcompeted by the WT cells upon infection. Increased expression of Blimp-1 and T-bet, cell cycle inhibitors, and proapoptotic genes was observed in the Menin-KO OT-1 Tg CD8+T cells upon infection. These data suggest that menin inhibits differentiation into terminal effectors and positively controls proliferation and survival of Ag-specific CD8+T cells that are activated upon infection. Collectively, our study uncovered an important role for menin in the immune response of CD8+T cells to infection.
authors: Department of Infection and Host Defenses, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; tyamada@m.ehime-u.ac.jp.
authors: Takeshi
authors: T
authors: Yamada
authors: Department of Infection and Host Defenses, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Makoto
authors: 0000-0003-0151-3556
authors: M
authors: Kanoh
authors: Department of Hematology, Clinical Immunology, and Infectious diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Shogo
authors: S
authors: Nabe
authors: Department of Obstetrics and Gynecology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Toshiaki
authors: 0000-0002-1435-0779
authors: T
authors: Yasuoka
authors: Department of Hematology, Clinical Immunology, and Infectious diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.|Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; and.|Translational Research Center, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Junpei
authors: J
authors: Suzuki
authors: Department of Infection and Host Defenses, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Akira
authors: A
authors: Matsumoto
authors: Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; and.|Translational Research Center, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Makoto
authors: M
authors: Kuwahara
authors: Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; and.
authors: Saho
authors: S
authors: Maruyama
authors: Department of Infection and Host Defenses, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Takuya
authors: T
authors: Fujimoto
authors: Department of Infection and Host Defenses, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Ryo
authors: R
authors: Sakisuka
authors: Department of Hematology, Clinical Immunology, and Infectious diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Masaki
authors: 0000-0002-1538-433X
authors: M
authors: Yasukawa
authors: Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan; and.|Translational Research Center, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Masakatsu
authors: M
authors: Yamashita
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000098815:T-bet Transcription Factor
chemical_list: C484898:Men1 protein, mouse; C513258:Prdm1 protein, mouse; D011518:Proto-Oncogene Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D010047:Ovalbumin; D000074462:Positive Regulatory Domain I-Binding Factor 1