title: Unexpected positive control of NFκB and miR-155 by DGKα and ζ ensures effector and memory CD8+ T cell differentiation.
abstract: Signals from the T-cell receptor (TCR) and γ-chain cytokine receptors play crucial roles in initiating activation and effector/memory differentiation of CD8 T-cells. We report here that simultaneous deletion of both diacylglycerol kinase (DGK) α and ζ (DKO) severely impaired expansion of CD8 effector T cells and formation of memory CD8 T-cells after Listeria monocytogenes infection. Moreover, ablation of both DGKα and ζ in preformed memory CD8 T-cells triggered death and impaired homeostatic proliferation of these cells. DKO CD8 T-cells were impaired in priming due to decreased expression of chemokine receptors and migration to the draining lymph nodes. Moreover, DKO CD8 T-cells were unexpectedly defective in NFκB-mediated miR-155 transcript, leading to excessive SOCS1 expression and impaired γ-chain cytokine signaling. Our data identified a DGK-NFκB-miR-155-SOCS1 axis that bridges TCR and γ-chain cytokine signaling for robust CD8 T-cell primary and memory responses to bacterial infection.
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Jialong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Sruti
authors.initials: S
authors.lastname: Krishna
authors.affiliation: School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jinli
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.|Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.|School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Danli
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Balachandra
authors.initials: B
authors.lastname: Gorentla
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Rick
authors.initials: R
authors.lastname: Huang
authors.affiliation: School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.|Department of Immunology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhong
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D019852:Diacylglycerol Kinase / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016328:NF-kappa B; D019852:Diacylglycerol Kinase; C512480:diacylglycerol kinase zeta, mouse
keywords: CD8 T cell; DGK; Immune response; Immunity; Immunology and Microbiology Section; Listeria monocytogenes; NFκB; miR-155