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Immunomodulatory effects of glucocorticoid-induced leucine zipper (GILZ) expression in murine bone-marrow derived macrophages.

ABSTRACT: Here, we provide evidence for the immunomodulatory effects of glucocorticoid-induced leucine zipper (GILZ) overexpression in macrophages, demonstrating enhanced antibacterial activity, protection from pyroptosis, and altered mitochondrial function. Additionally, our findings reveal a significant impact on MMP activity, suggesting a role for GILZ in influencing extracellular matrix remodeling and wound healing processes. The study contributes to explorations of GILZ in its significance in pro-resolving macrophage functions.

ORGANISM(S): Mus musculus

PROVIDER: GSE254137 | GEO | 2024/05/13

REPOSITORIES: GEO

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Immunomodulatory effects of glucocorticoid-induced leucine zipper (GILZ) expression in murine bone-marrow derived macrophages.

Project description:Immunomodulatory effects of glucocorticoid-induced leucine zipper (GILZ) expression in murine bone-marrow derived macrophages.

| PRJNA1068618 | ENA

Identification of Glucocorticoid-Induced Leucine Zipper (Gilz) gene targets in undifferentiated spermatogonia

Project description:Identification of Glucocorticoid-Induced Leucine Zipper (Gilz) gene targets in undifferentiated spermatogonia

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Identification of Glucocorticoid-Induced Leucine Zipper (Gilz) gene targets in undifferentiated spermatogonia

Project description:Sustained spermatogenesis in adult males and recovery of fertility following germ cell depletion are dependent on undifferentiated spermatogonia with self-renewal potential. We have previously demonstrated a critical cell-autonomous role for Gilz in spermatogonial stem cell maintainance and spermatogenesis. To identify genes regulated by Gilz in the male germline, we have isolated undifferentiated spermatogonial cells from tamoxifen treated Gilzflox/flox (Control) and Gilzflox/flox UBC-CreER (TAM-KO) mice that will allow identification of genes mis-expressed upon loss of GILZ.

2018-08-24 | GSE107893 | GEO

Intricate coupling between the transactivation and basic-leucine zipper domains governs the CK2-dependent phosphorylation of ATF4

Project description:Most transcription factors possess at least one long intrinsically disordered transactivation domain that binds to a variety of co-activators and co-repressors and plays a key role in modulating the transcriptional activity. Despite the crucial importance of these mechanisms, the structural and functional basis of transactivation domain in yet poorly understood. Here, we focused on ATF4/CREB-2, an essential transcription factor for cellular stress adaptation. We found that the N-terminal region of the transactivation domain is involved in transient long-range interactions with the basic-leucine zipper domain. In vitro phosphorylation assays with the protein kinase CK2 show that the presence of the basic-leucine zipper domain is required for optimal phosphorylation of the transactivation domain. This study uncovers the intricate coupling existing between the transactivation and basic-leucine zipper domains of ATF4 and highlights its potential functional relevance.

2023-03-11 | PXD029704 | Pride

Deep mutational scanning of the interaction of JUN's leucine zipper domain and other human bZIPs in different experimental conditions

Project description:Deep mutational scanning of the interaction of JUN's leucine zipper domain and other human bZIPs in different experimental conditions

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Leucine zipper-based sorting system enables generation of multi-functional CAR T cells

Project description:Resistance to chimeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms including antigen-loss escape and tumor-induced immune suppression. Expression of multiple CARs may overcome multi-antigen-loss escape. Similarly, expression of switch receptors that convert inhibitory immune checkpoint signals into positive costimulatory signals may enhance CAR T cell activity in the tumor microenvironment. Engineering multiple features into one cell product, however, is limited by transgene packaging constraints of current vector systems. Here, we describe a leucine zipper-based cell sorting methodology that enables selective single-step immunomagnetic purification of cells co-transduced with two vectors, designed to potentially double the number of incorporated transgenes. This “Zip-sorting” system facilitated generation of T cells simultaneously expressing up to four CARs and co-expressing up to three switch receptors. These multi-CAR multi-Switch receptor arrays enabled T cells to eliminate antigenically heterogeneous syngeneic leukemia populations co-expressing multiple inhibitory ligands. Zip-sorted multi-CAR multi-Switch receptor T cells represent a combinatorial therapeutic strategy to overcome multiple mechanisms of CAR T cell resistance.

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Leucine zipper-based sorting system enables generation of multi-functional CAR T cells

Project description:Leucine zipper-based sorting system enables generation of multi-functional CAR T cells

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A heterospecific leucine zipper tetramer.

Project description:Protein-protein interactions play an essential role in the assembly of the macromolecular complexes that form functional networks and control cellular behavior. Elucidating principles of molecular recognition governing potentially complex interfaces is a challenging goal for structural and systems biology. Extensive studies of alpha-helical coiled coils have provided fundamental insight into the determinants of one seemingly tractable class of oligomeric protein interfaces. We report here that two different valine-containing mutants of the GCN4 leucine zipper that fold individually as four-stranded coiled coils associate preferentially in mixtures to form an antiparallel, heterotetrameric structure. X-ray crystallographic analysis reveals that the coinciding hydrophobic interfaces of the hetero- and homotetramers differ in detail, thereby controlling their partnering and structural specificity. Equilibrium disulfide exchange and thermal denaturation experiments show that the 50-fold preference for heterospecificity is determined by interfacial van der Waals interactions and hydrophobicity. Parallel studies of two alanine-containing variants confirm the above-mentioned interpretation of the basis and mechanism of this heterospecificity. Our results suggest that coiled-coil recognition is an inherently geometric process in which heterotypic interaction specificity derives from a complementarity of both shape and chemistry.

| S-EPMC7111190 | biostudies-literature

Immunomodulatory-Photodynamic Nanostimulators for Invoking Pyroptosis to Augment Tumor Immunotherapy

Project description:Acidic tumor microenvironment (TME)-evoked MRC nanoparticles (MRC NPs) co-delivering immune agonist RGX-104 and photosensitizer chlorine e6 (Ce6) are reported for pyroptosis-mediated immunotherapy. RGX-104 remodels TME by transcriptional activation of ApoE to regress myeloid-derived suppressor cells’ (MDSCs) activity, which neatly creates foreshadowing for intensifying pyroptosis. Considering Ce6-triggered photodynamic therapy (PDT) can strengthen oxidative stress and organelles destruction to increase immunogenicity, immunomodulatory-photodynamic MRC nanodrugs will implement an aforementioned two-pronged strategy to enhance gasdermin E (GSDME)-dependent pyroptosis. RNA-seq analysis of MRC at the cellular level is introduced to first elucidate the intimate relationship between RGX-104 acting on LXR/ApoE axis and pyroptosis, where RGX-104 provides the prerequisite for pyroptosis participating in antitumor therapy. Briefly, MRC with favorable biocompatibility tackles the obstacle of hydrophobic drugs delivery, and becomes a powerful pyroptosis inducer to reinforce immune efficacy. MRC-elicited pyroptosis in combination with anti-PD-1 blockade therapy boosts immune response in solid tumors, successfully arresting invasive metastasis and extending survival based on remarkable antitumor immunity. MRC may initiate a new window for immuno-photo pyroptosis stimulators augmenting pyroptosis-based immunotherapy. Owing to the transcriptome sequencing on 4T1 cells exposed to various treatment, pyroptosis mechanism of MRC was thoroughly analyzed via comparing the expression discrepancy among PBS, MRC, and MRC+L groups.

2023-08-13 | GSE240328 | GEO

The Cytoskeletal Stress Response Pathway: a homeostatic system driven by Dual Leucine Zipper Kinase (DLK)

Project description:Injury to peripheral axons initiates a complex cascade of cellular responses, including cytoskeletal disassembly, axon transport disruption, and ultimately axon regeneration. Central to this process is the MAP triple kinase Dual-Leucine Zipper Kinase (DLK), activated by injury and other neuronal stressors. Here, we propose the existence of a homeostatic mechanism termed the Cytoskeletal Perturbation Response (CPR). We investigate this hypothesis by examining the response of cultured dorsal root ganglion (DRG) neurons to low dose nocodazole treatment, a cytoskeletal perturbing agent. To gain insights into DLK-dependent transcriptional changes following cytoskeletal insult, we performed bulk RNA sequencing on cultured neurons treated for 16 hours. Using a fully crossed two-factor design, we determined the interactive effect of DLK on nocodazole- dependent transcriptional changes. Our study demonstrates that cytoskeletal perturbation triggers DLK-dependent signaling cascades, leading to significant transcriptional changes. These changes involve transcription factors (Jun, Egr1, Atf3) and MAP kinase regulators (DUSPs), pointing to a regulatory network that attenuates DLK signaling. Taken together, our findings suggest that cytoskeletal perturbation activates a DLK-dependent homeostatic mechanism, the CPR, which orchestrates transcriptional changes and morphological adaptations to repair neuronal damage. The CPR bears similarities to established homeostatic responses, offering insights into the intricate processes that underlie axon regeneration and cellular repair.

2023-10-11 | GSE244883 | GEO

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