TAOK3, a Regulator of LCK–SHP-1 Crosstalk during TCR Signaling

Ormonde, João V S; Nie, Yan; Madrenas, Joaquı́n

doi:10.1615/critrevimmunol.2019030480

Cited by 5 publications

(3 citation statements)

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“…Conversely, CD45+ cells from the brain exhibited enriched T cell gene signatures. These included higher expression of transcripts associated with the T cell receptor α constant gene (TRAC), genes involved in TCR signaling (TAOK3, Sos1) (17) (18), genes regulating T cell metabolism (ERN1 and TXNIP (19), and genes linked to effector and central memory T cell programs (HSP70, DNAJB1, HSPH1, GZMA, NKG7, ID2, HELIOS (encoded by IKZF2), homeobox only protein (HOPX), and IL-7R (20) (21) (22). Additionally, the expression of the trafficking factor ITGβ2 suggested LFA-1 mediated T cell migration across the blood-brain barrier.…”

Section: Single-cell Transcriptomic Analysis Of Cd45+ Leukocytes Iden...mentioning

confidence: 99%

CCR7+ CD4 T Cell Immunosurveillance Disrupted in Chronic SIV-Induced Neuroinflammation in Rhesus Brain

Elizaldi,

Hawes,

Verma

et al. 2023

Preprint

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CD4 T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4 T cells resembling lymph node central memory (TCM) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of TCM. Brain CCR7+ CD4 T cells exhibited recall proliferation and interleukin-2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside other CNS border tissues. Sequestering TCM cells in lymph nodes using FTY720 led to reduced CCR7+ CD4 T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL57 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain CCR7+ CD4 T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for CCR7+ CD4 T cells in CNS immune surveillance and their decline during chronic SIV-induced neuroinflammation highlights their responsiveness to neuroinflammatory processes.

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Section: Single-cell Transcriptomic Analysis Of Cd45+ Leukocytes Iden...mentioning

confidence: 99%

CCR7+ CD4 T Cell Immunosurveillance Disrupted in Chronic SIV-Induced Neuroinflammation in Rhesus Brain

Elizaldi,

Hawes,

Verma

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Despite its relative novelty being comparable to similarly scored MAP3K16 and MAP3K17, TAOK3 is not an IDGeligible kinase. Existing literature identifies TAOK3 as a contributing regulator of osteoblast differentiation and skeletal mineralization, lipid partitioning in the liver, and t-cell receptor signaling [136][137][138][139]. Furthermore, TAOK3 has also been identified to regulate cancer stem-cells in pancreatic cancer and enhance microtubule-targeted drug resistance in breast cancer through NF-κB signaling [140,141].…”

Section: Map3k18 (Taok3)mentioning

confidence: 99%

MAP3K Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types

Nguyen¹,

Tran²,

Rivera³

et al. 2022

Front. Biosci. (Landmark Ed)

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“…Accordingly, both the gut microbiota and immune system are implicated in the etiopathogenesis or manifestation of NDDs (Fung et al, 2017). TAO kinases were reported to regulate immunity (Ormonde et al, 2018(Ormonde et al, , 2019Zhang et al, 2018), gut development (Huang et al, 2014) and likely in maintenance of microbiota integration since MAPKs are involved (Thomas and Versalovic, 2010). Thus, the possible non-neurological role of TAO kinases in NDDs should be seriously considered.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Clinical and Neurobiological Aspects of TAO Kinase Family in Neurodevelopmental Disorders

Pan

Yang

et al. 2021

Front. Mol. Neurosci.

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Despite the complexity of neurodevelopmental disorders (NDDs), from their genotype to phenotype, in the last few decades substantial progress has been made in understanding their pathophysiology. Recent accumulating evidence shows the relevance of genetic variants in thousand and one (TAO) kinases as major contributors to several NDDs. Although it is well-known that TAO kinases are a highly conserved family of STE20 kinase and play important roles in multiple biological processes, the emerging roles of TAO kinases in neurodevelopment and NDDs have yet to be intensively discussed. In this review article, we summarize the potential roles of the TAO kinases based on structural and biochemical analyses, present the genetic data from clinical investigations, and assess the mechanistic link between the mutations of TAO kinases, neuropathology, and behavioral impairment in NDDs. We then offer potential perspectives from basic research to clinical therapies, which may contribute to fully understanding how TAO kinases are involved in NDDs.

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TAOK3, a Regulator of LCK–SHP-1 Crosstalk during TCR Signaling

Cited by 5 publications

References 0 publications

CCR7+ CD4 T Cell Immunosurveillance Disrupted in Chronic SIV-Induced Neuroinflammation in Rhesus Brain

CCR7+ CD4 T Cell Immunosurveillance Disrupted in Chronic SIV-Induced Neuroinflammation in Rhesus Brain

MAP3K Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types

Clinical and Neurobiological Aspects of TAO Kinase Family in Neurodevelopmental Disorders

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