JunB Is Critical for Survival of T Helper Cells

Hsieh, Tsung Han; Sasaki, Daizo; Taira, Naoyuki; Chien, Hsiaochiao; Sarkar, Shukla; Seto, Yu; Miyagi, Mio; Ishikawa, Hiroki

doi:10.3389/fimmu.2022.901030

Cited by 15 publications

(5 citation statements)

References 40 publications

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“…Of note, VSV-G-pseudotyped lentivirus is capable of infecting CEM-T4 cells. However, the death of all CEM-T4 cells that initially survived puromycin selection supports prior data demonstrating the importance of JunB in the expansion and survival of T-cell populations ( Hsieh et al, 2021 , 2022 ). We further attempted knockdown of JunB expression using siRNA in both Jurkat and CEM-T4 cells.…”

Section: Discussionsupporting

confidence: 82%

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Genome-wide CRISPR/Cas9 screen reveals JunB downmodulation of HIV co-receptor CXCR4

Schulze,

Gregory,

Johnson

et al. 2024

Front. Microbiol.

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HIV-1 relies extensively on host cell machinery for replication. Identification and characterization of these host-virus interactions is vital to our understanding of viral replication and the consequences of infection in cells. Several prior screens have identified host factors important for HIV replication but with limited replication of findings, likely due to differences in experimental design and conditions. Thus, unidentified factors likely exist. To identify novel host factors required for HIV-1 infection, we performed a genome-wide CRISPR/Cas9 screen using HIV-induced cell death as a partitioning method. We created a gene knockout library in TZM-GFP reporter cells using GeCKOv2, which targets 19,050 genes, and infected the library with a lethal dose of HIV-1NL4-3. We hypothesized that cells with a knockout of a gene critical for HIV infection would survive while cells with a knockout of a non-consequential gene would undergo HIV-induced death and be lost from the population. Surviving cells were analyzed by high throughput sequencing of the integrated CRISPR/Cas9 cassette to identify the gene knockout. Of the gene targets, an overwhelming majority of the surviving cells harbored the guide sequence for the AP-1 transcription factor family protein, JunB. Upon the generation of a clonal JunB knockout cell line, we found that HIV-1NL4-3 infection was blocked in the absence of JunB. The phenotype resulted from downregulation of CXCR4, as infection levels were recovered by reintroduction of CXCR4 in JunB KO cells. Thus, JunB downmodulates CXCR4 expression in TZM-GFP cells, reducing CXCR4-tropic HIV infection.

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Section: Discussionsupporting

confidence: 82%

“…We also attempted to perform siRNA knockdown of JunB in the Jurkat and CEM-T4 T cell lines but were unable to achieve knockdown. Collectively, these negative findings support prior studies that have highlighted the importance of JunB in T cells (Koizumi et al, 2018;Hsieh et al, 2021Hsieh et al, , 2022.…”

Section: Generation Of a Tzm-gfp Junb Knockout Cell Linesupporting

confidence: 89%

Genome-wide CRISPR/Cas9 screen reveals JunB downmodulation of HIV co-receptor CXCR4

Schulze,

Gregory,

Johnson

et al. 2024

Front. Microbiol.

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“…Processed data of CD8 BATF, IRF4 and JunB ChIP-seq data were sourced from GSE111902. Raw sequencing CUT&RUN data of CD8 IgG and Tox were downloaded from GSE175437 ( 16 ); CD4 BATF, IRF4 and JunB ChIP-seq data was obtained from GSE172490 ( 17 ). Sequenced reads were aligned to mm10 using Bowtie ( 18 ) with parameters “–chunkmbs 1000 -S -p 10 -m 1”.…”

Section: Methodsmentioning

confidence: 99%

Tox induces T cell IL-10 production in a BATF-dependent manner

Canaria,

Rodriguez,

Wang

et al. 2023

Front. Immunol.

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Tox is a member of the high mobility group (HMG)-Box transcription factors and plays important roles in thymic T cell development. Outside of the thymus, however, Tox is also highly expressed by CD8 and CD4 T cells in various states of activation and in settings of cancer and autoimmune disease. In CD4 T cells, Tox has been primarily studied in T follicular helper (TFH) cells where it, along with Tox2, promotes TFH differentiation by regulating key TFH-associated genes and suppressing CD4 cytotoxic T cell differentiation. However, the role of Tox in other T helper (Th) cell subtypes is less clear. Here, we show that Tox is expressed in several physiologically-activated Th subtypes and its ectopic expression enhances the in vitro differentiation of Th2 and T regulatory (Treg) cells. Tox overexpression in unpolarized Th cells also induced the expression of several genes involved in cell activation (Pdcd1), cellular trafficking (Ccl3, Ccl4, Xcl1) and suppressing inflammation (Il10) across multiple Th subtypes. We found that Tox binds the regulatory regions of these genes along with the transcription factors BATF, IRF4, and JunB and that Tox-induced expression of IL-10, but not PD-1, is BATF-dependent. Based on these data, we propose a model where Tox regulates Th cell chemotactic genes involved in facilitating dendritic cell-T cell interactions and aids in the resolution or prevention of inflammation through the production of IL-10.

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“…Most recently, Hsieh et al. found that JunB plays a key role in the clonal proliferation of a variety of T helper cells by inhibiting their apoptosis ( Hsieh et al., 2022 ). Therefore, JunB is essential for the survival and differentiation of Th2 cells and Th2-mediated autoimmune diseases.…”

Section: The Key Role Of Junb In Immune Responsementioning

confidence: 99%

“…Functionally, USP38 was necessary for production of Th2 cytokines (IL-4, IL-5 and IL-13) induced by TCR, and mice with USP38 knockout were refractory to asthma induced by OVA or HDM (Chen et al, 2018). Most recently, Hsieh et al found that JunB plays a key role in the clonal proliferation of a variety of T helper cells by inhibiting their apoptosis (Hsieh et al, 2022). Therefore, JunB is essential for the survival and differentiation of Th2 cells and Th2mediated autoimmune diseases.…”

Section: Adaptive Immunitymentioning

confidence: 99%

JunB: a paradigm for Jun family in immune response and cancer

Ren,

Cai,

Yao

et al. 2023

Front. Cell. Infect. Microbiol.

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Jun B proto-oncogene (JunB) is a crucial member of dimeric activator protein-1 (AP-1) complex, which plays a significant role in various physiological processes, such as placental formation, cardiovascular development, myelopoiesis, angiogenesis, endochondral ossification and epidermis tissue homeostasis. Additionally, it has been reported that JunB has great regulatory functions in innate and adaptive immune responses by regulating the differentiation and cytokine secretion of immune cells including T cells, dendritic cells and macrophages, while also facilitating the effector of neutrophils and natural killer cells. Furthermore, a growing body of studies have shown that JunB is involved in tumorigenesis through regulating cell proliferation, differentiation, senescence and metastasis, particularly affecting the tumor microenvironment through transcriptional promotion or suppression of oncogenes in tumor cells or immune cells. This review summarizes the physiological function of JunB, its immune regulatory function, and its contribution to tumorigenesis, especially focusing on its regulatory mechanisms within tumor-associated immune processes.

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JunB Is Critical for Survival of T Helper Cells

Cited by 15 publications

References 40 publications

Genome-wide CRISPR/Cas9 screen reveals JunB downmodulation of HIV co-receptor CXCR4

Genome-wide CRISPR/Cas9 screen reveals JunB downmodulation of HIV co-receptor CXCR4

Tox induces T cell IL-10 production in a BATF-dependent manner

JunB: a paradigm for Jun family in immune response and cancer

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