Cytokine-like Molecule CCDC134 Contributes to CD8+ T-cell Effector Functions in Cancer Immunotherapy

Huang, Jing; Xiao, Lin; Gong, Xiaoting; Shao, Wenwei; Yin, Yuqin; Liao, Qinyuan; Yang, Meng; Zhang, Yingmei; Ma, Dalong; Qiu, Xiaoyan

doi:10.1158/0008-5472.can-13-3132

Cited by 20 publications

(21 citation statements)

References 38 publications

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“…The cytokine-like gene Ccdc134 →Il4!,Irf4!,Gata3 is also a major hit. It has so far received little attention in the literature, but has been linked to arthritis 31 and shown to promote CD8+ T cell effector functions 32 . In short, we have discovered many new genes with a broad effect on Th2 differentiation that deserve further investigation.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide CRISPR screens in T helper cells reveal pervasive cross-talk between activation and differentiation

Henriksson

Chen

Gomes

et al. 2017

Preprint

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T helper type 2 (Th2) cells are important regulators of mammalian adaptive immunity and have relevance for infection, auto-immunity and tumour immunology. Using a newly developed, genome-wide retroviral CRISPR knock-out (KO) library, combined with RNA-seq, ATAC-seq and ChIP-seq, we have dissected the regulatory circuitry governing activation (including proliferation) and differentiation of these cells. Our experiments distinguish cell activation versus differentiation in a quantitative framework. We demonstrate that these two processes are tightly coupled and are jointly controlled by many transcription factors, metabolic genes and cytokine/receptor pairs. There is only a small number of genes regulating differentiation without any role in activation. Our study provides an atlas for the T helper cell regulatory network, pinpointing key players of Th2 differentiation and demonstrating remarkable plasticity between the diverse T helper cell fates. We provide an online resource for interactive data querying at: http://data.teichlab.org.

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Section: Introductionmentioning

confidence: 99%

Genome-wide CRISPR screens in T helper cells reveal pervasive cross-talk between activation and differentiation

Henriksson

Chen

Gomes

et al. 2017

Preprint

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“…Consistently, rat embryonic cortical neurons showed a marked increase in survival when co-cultured with NG2 glia or exposed to their CM [94,95]. Further, the CM of NG2 glia displayed remarkable pro-angiogenic effects by stimulating proliferation, tip sprouting, tube formation, and expressions of tight-junctions proteins in endothelial cells [65,96,97] and promoting proliferation/survival of pericytes [66]. In contrast, the CM obtained from NG2 glia exposed to inflammatory cytokines weakened endothelial barrier tightness in vitro [67].…”

Section: Ng2 Glia-derived Signals Can Modulate Neuronal and Non-neuromentioning

confidence: 75%

“…study of cultured mouse NG2 glia and expr. in adult mouse NG2 glia in vivo [87] NG2 glia modulation of glutamatergic neurotransmission and astrocytic extracellular glutamate uptake [87], neuronal protection and CNS repair [101], modulation of synaptic plasticity [102] and astroglial and microglial reactivity [103] Platelet-derived growth factor AA, PDGF-AA CM of cultured mouse NG2 glia [97] Neuronal protection [104], synaptic plasticity [105] and angiogenesis [106] Platelet-derived growth factor BB, PDGF-BB CM of cultured mouse NG2 glia [97] Neurotrophic and neuroregulatory functions [107], synaptic plasticity [105] Vascular endothelial growth factor, VEGF CM of cultured mouse NG2 glia [97] Neurotrophic function [108,109], regulation of adult neurogenesis [108] Insulin-like growth factor 1, IGF-1 CM of cultured rat NG2 glia [94]; Gene expr. study of cultured rat NG2 glia [93] Synaptic maturation [110] Hepatocyte growth factor, HGF In vivo expr.…”

Section: Growth Factorsmentioning

confidence: 99%

“…study of freshly sorted mouse NG2 glia [131] Neuronal survival [191] C-X-C Motif Chemokine Ligand 10, CxCl1 Gene expr. study of cultured mouse NG2 glia exposed to Il17 or Tnf [158,192] Neuroinflammation [193] C-X-C Motif Chemokine Ligand 10, CxCl10 CM of cultured mouse NG2 glia [97] Neuroinflammation [194] C-X3-C Motif Chemokine Ligand 1, Cx3Cl1 CM of cultured mouse NG2 glia [97] Regulation of synapses activity and plasticity, brain functional connectivity and adult hippocampal neurogenesis [195] C-C Motif Chemokine Ligand 7, Ccl7 Gene expr. study of cultured mouse NG2 glia exposed to Il17 [192] Neuroinflammation [196][197][198] Granulocyte-Macrophage Colony Stimulating Factor, GM-CSF or Csf2…”

Section: Neuregulinsmentioning

confidence: 99%

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NG2 Glia: Novel Roles beyond Re-/Myelination

Parolisi

Boda

2018

Neuroglia

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Neuron-glia antigen 2-expressing glial cells (NG2 glia) serve as oligodendrocyte progenitors during development and adulthood. However, recent studies have shown that these cells represent not only a transitional stage along the oligodendroglial lineage, but also constitute a specific cell type endowed with typical properties and functions. Namely, NG2 glia (or subsets of NG2 glia) establish physical and functional interactions with neurons and other central nervous system (CNS) cell types, that allow them to constantly monitor the surrounding neuropil. In addition to operating as sensors, NG2 glia have features that are expected for active modulators of neuronal activity, including the expression and release of a battery of neuromodulatory and neuroprotective factors. Consistently, cell ablation strategies targeting NG2 glia demonstrate that, beyond their role in myelination, these cells contribute to CNS homeostasis and development. In this review, we summarize and discuss the advancements achieved over recent years toward the understanding of such functions, and propose novel approaches for further investigations aimed at elucidating the multifaceted roles of NG2 glia.

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“…CCDC134 was proposed to have immune cytokine function, and directly promoted CD8 + T-cell activation, proliferation and cytotoxicity ( 3 ). Additionally, CCDC134 demonstrated its potent antitumor effects by augmenting CD8 + T-cell-mediated immunity ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

CCDC134 serves a crucial role in embryonic development

Zhang

Xia

et al. 2017

Int J Mol Med

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Coiled-coil domain containing 134 (CCDC134), a characterized secreted protein, may serve as an immune cytokine and illustrates its potent antitumor effects by augmenting CD8+ T-cell-mediated immunity. Additionally, CCDC134 may also act as a novel regulator of human alteration/deficiency in activation 2a, and be involved in the p300-CBP-associated factor complex and affect its acetyltransferase activity. To clarify the biological and pathological function of CCDC134, the present study generated a viable and fertile Ccdc134fl/fl mouse strain that allowed temporal and spatial control of gene ablation. Ccdc134−/− embryos generated by crossing of Ccdc134fl/fl mice with human β-actin-Cre or zona pellucida 3-Cre transgenic mice were embryonic lethal from embryonic day (E)12.5 to birth. Ccdc134 loss was associated with severe hemorrhages in the brain ventricular space and neural tube, pale and abnormal livers, cardiac hypertrophy and placental distress. Furthermore, it was demonstrated that a fraction of E13.5 fetal livers and brains exhibited reduced cell proliferation and vascular endothelial cell defects. CCDC134 also exhibited a dynamic and specific expression pattern during embryo development. The present results suggest that Ccdc134 may have specific biological functions in regulating mouse embryonic development.

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Cytokine-like Molecule CCDC134 Contributes to CD8+ T-cell Effector Functions in Cancer Immunotherapy

Cited by 20 publications

References 38 publications

Genome-wide CRISPR screens in T helper cells reveal pervasive cross-talk between activation and differentiation

Genome-wide CRISPR screens in T helper cells reveal pervasive cross-talk between activation and differentiation

NG2 Glia: Novel Roles beyond Re-/Myelination

CCDC134 serves a crucial role in embryonic development

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