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The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity [RNA-Seq]

ABSTRACT: Aberrant activated T cell infiltration is a key driver of autoimmune pathogenesis, highlighting the therapeutic potential of inhibiting T cell migration. However, the regulatory mechanisms governing tissue ingress of antigen-specific T cells remain elusive. Here, we report that SUB1, a transcription factor upregulated in CD4+ T cells from patients with autoimmune disorders, is regulated by the TCR–IRF4 axis. SUB1 deficiency diminished DOCK2 expression by 50%, impairing Rac-dependent actin polymerization and T cell migration, and consequently suppressed the onset of experimental autoimmune encephalomyelitis (EAE). Mechanistically, SUB1 promotes chromatin accessibility at the Junb and Dock2 loci via liquid–liquid phase separation (LLPS), facilitating biomolecular condensate formation. Furthermore, SUB1 directly activates Junb transcription and cooperates with JUNB to enhance Dock2 expression. Our results identify SUB1 as a critical regulator of antigen-specific CD4+ T cell migration and propose it as a promising therapeutic target for autoimmune diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE308746 | GEO | 2026/02/01

REPOSITORIES: GEO

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The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity

Project description:Aberrant activated T cell infiltration is a key driver of autoimmune pathogenesis, highlighting the therapeutic potential of inhibiting T cell migration. However, the regulatory mechanisms governing tissue ingress of antigen-specific T cells remain elusive. Here, we report that SUB1, a transcription factor upregulated in CD4+ T cells from patients with autoimmune disorders, is regulated by the TCR–IRF4 axis. SUB1 deficiency diminished DOCK2 expression by 50%, impairing Rac-dependent actin polymerization and T cell migration, and consequently suppressed the onset of experimental autoimmune encephalomyelitis (EAE). Mechanistically, SUB1 promotes chromatin accessibility at the Junb and Dock2 loci via liquid–liquid phase separation (LLPS), facilitating biomolecular condensate formation. Furthermore, SUB1 directly activates Junb transcription and cooperates with JUNB to enhance Dock2 expression. Our results identify SUB1 as a critical regulator of antigen-specific CD4+ T cell migration and propose it as a promising therapeutic target for autoimmune diseases.

2026-02-01 | GSE309052 | GEO

The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity [ATAC-Seq]

2026-02-01 | GSE308747 | GEO

Effect of SUB1 knockdown on aggressive prostate cancer

Project description:SUB1 is known to be playing critical role in vital cellular processes such as DNA replication, repair and heterochromatization. Expression profiling studies in several cancers show its overexpression. However, its regulation and function in cancer has been less explored. Our study has indicated high expression of SUB1 in aggressive prostate cancer, we also found that the knockdown of SUB1 led to alterations in cell proliferation, invasion and migration. In addition, we found that mir-101, a tumor suppressor microRNA targets and regulates the expression of SUB1

2016-10-31 | GSE74895 | GEO

Single-cell transcriptomics reveals a pivotal role of DOCK2 in Sjögren’s disease

Project description:Sjögren's disease (SjD) is an autoimmune condition characterized by the dysfunction of the salivary and lacrimal glands. The study aimed to decipher the pathogenic cell populations and their immunological pathways in the salivary glands. We further determined the therapeutic effect of inhibiting DOCK2 shared by novel clusters of CD8Cd8+ T cells in a SjD mouse model.

2024-12-19 | GSE268532 | GEO

The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity

Project description:The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity

| PRJNA1333869 | ENA

Comparison of gene expression profiles in naïve WT and Asc-null bone marrow derived dendritic cells

Project description:The adaptor protein ASC contributes to innate immunity through the assembly of caspase-1-activating inflammasome complexes. We demonstrate that ASC plays an inflammasome-independent cell-intrinsic role in adaptive immune cells. Asc-/- mice displayed defective antigen presentation by dendritic cells and lymphocyte migration due to impaired Rac-mediated actin polymerization. Genome-wide analysis showed that ASC, but not Nlrp3 or caspase-1, controls mRNA stability and expression of DOCK2, a guanine nucleotide exchange factor that mediates Rac-dependent signaling in immune cells. DOCK2-deficient dendritic cells showed similar defective antigen uptake as Asc-/- cells. Ectopic expression of DOCK2 in ASC-deficient cells restored Rac-mediated actin polymerization, antigen uptake and chemotaxis. Thus, ASC shapes adaptive immunity independently of inflammasomes by modulating DOCK2-dependent Rac activation and F-actin polymerization in dendritic cells and lymphocytes. Three replicates of naïve WT and three replicates of Asc-/- bone marrow derived dendritic cells were analyzed on the Affymetrix HT MG-430 PM plate array.

2012-07-08 | E-GEOD-30769 | biostudies-arrayexpress

DOCK2 protects against bacterial sepsis by constraining T helper 1 response

Project description:Sepsis is a systemic host response to infection with life-threatening consequence, which ranks among the top 10 causes of death worldwide. Nevertheless, our understanding of the molecular and cellular impact of sepsis remains rudimentary. Here, we identified dedicator of cytokinesis 2 (DOCK2) is a critical downregulating factor for lipopolysaccharide (LPS) signal pathways. DOCK2-deficient mice were highly sensitive to LPS-induced sepsis and Escherichia coli sepsis with increased levels of inflammatory cytokines, especially interferon-g (IFN-g), which were mainly due to hyperresponsive T helper 1 (Th1) cells. Ulteriorly, we verified the vital role of DOCK2-mediated Th1 cells in sepsis by neutralizing both IFN-g and CD4 and found both of which blockade reduced the severity of sepsis in Dock2-/- mice. Mechanically, DOCK2-mediated cell cycle progression and cytokine signaling act in concert to govern peripheral Th1 cell fate. Taken together, our data indicate that DOCK2 acts as a protective role in regulating systemic inflammation and multi-organ injury in bacterial sepsis by constraining Th1 response.

2025-05-22 | GSE297913 | GEO

The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity [ATAC-Seq]

Project description:The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity [ATAC-Seq]

| PRJNA1332637 | ENA

The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity [RNA-Seq]

Project description:The TCR-SUB1-DOCK2 Signaling Axis Governs Autoimmunity by Regulating CD4+ T Cell Migratory Capacity [RNA-Seq]

| PRJNA1332638 | ENA

Sub1 occupancy in yeast cells in exponential growth condition

Project description:A genome-wide location analysis by ChIP on chip of the gene occupancy by Sub1 was undertaken to define the gene targets of Sub1 in vivo. Chromatin immunoprecipitation (ChIP) assays were performed on epitope-tagged Sub1-3HA cross-linked chromatin from exponentially growing cells. Immunopurified DNA and DNA from whole-cell extracts were fluorescently labelled and competitively hybridized to DNA microarrays harbouring ORFs and intergenic regions. The ratio of fluorescence intensities at each site in the microarray provided a measure of the extent of Sub1 binding to a specific genomic locus. Data from three independent experiments were compiled. Many loci were found to be significantly enriched in active growth conditions where Sub1 is not essential for cell viability. Approximately one-fourth of the enriched loci were located within ORF and the others corresponded to intergenic regions and to genes encoding non-translated RNAs. The ACT1, PMA1, PYK1, ADH1 and snoRNA genes previously identified as DNA targets of Sub1 were indeed enriched in our data. Sub1 was also preferentially bound to a subset of Pol II-transcribed genes encoding constituents of the cell wall, the nucleosome and the ribosome. Remarkably, these Pol II genes represented only two-third of the enriched loci. The other ones corresponded to Pol III-transcribed genes present on the arrays or to the intergenic regions and ORFs adjacent to these genes, suggesting the association of Sub1 to all Pol III-transcribed genes in conditions of active growth. The arrays used had a poor coverage of the rDNA gene locus. Nevertheless, we found a significant enrichment of the different loci corresponding to that region suggesting that Sub1 associates at many locations throughout the rDNA gene. Altogether, the results suggested that Sub1 could be a regulator of all three transcription systems. Keywords: ChIP-Chip

2009-08-27 | GSE11054 | GEO

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