GPR183 (G Protein-Coupled Receptor 183)

In a murine MRSA pneumonia model, PTX-trained mice showed reduced bacterial burden, preserved lung barrier integrity, and enhanced immune activation, all of which were reversed by GPR183 inhibition or STING deficiency. Collectively, our findings uncover a previously unrecognized immunomodulatory function of PTX and highlight the therapeutic potential of targeting the GPR183-STING axis to enhance trained immunity against resistant bacterial infections.

We detail the quantitative expression profiles of these molecules on various subsets of leukocytes and provide validation data for these mAbs. The implications of these expression profiles are discussed for the potential therapeutic targeting of immune-mediated diseases and cancer.

In the mouse model, GPR183 significantly reduced metastatic burden. These findings suggest that GPR183 inhibits NSCLC visceral metastasis by modulating angiogenesis and metastatic pathways, presenting a potential therapeutic target for preventing brain metastasis in lung cancer patients.

Based on Perturb-seq and functional investigations, GPR183 also enhances effector functions, such that engineering NK and CAR NK cells to express GPR183 enhances their ability to migrate to, infiltrate, and control breast cancer tumors. Our study uncovered metabolite-based tumor immune recruitment mechanisms, opening avenues for spatially targeted cell therapies.

The results suggested that GPR183 may influence disease progression through the activation of the "TNFa Signaling Via NF-κB" pathway. Collectively, these findings suggested that GPR183 could serve as a valuable prognostic biomarker in CN-AML, offering insights into the underlying mechanisms of disease progression.

Finally, we demonstrate that LN CCL19 is critical in lymphocyte recruitment during inflammation. Thus, our work explains how naive precursor trafficking is sustained in responding LNs, identifies a role for oxysterols in cell recruitment into inflamed tissues, and establishes a logic for the CCR7 two-ligand system.

Furthermore, we explored missense mutations of pediatric ALL in relation to the RNA gene expression findings, providing insights into the genetic underpinnings of this disease. By integrating both RNA-seq and missense mutation data, this article aims to provide an insightful and broader perspective on the potential correlations between specific GPCR and their roles in pediatric ALL.

Certain oxidized steroids can increase both the number and activation of infiltrating T cells, synergizing with anti-PD-1 to enhance anti-tumor efficacy. An in-depth study of the biological mechanisms of oxidized sterols will not only enhance our understanding of the complexity of the tumor immune microenvironment but may also reveal new therapeutic targets, providing innovative strategies for tumor immunotherapy.

The new GPR18 agonists showed minimal species differences, while THC acted as a weak partial agonist at the mouse receptor. The newly discovered compounds represent the most potent and selective GPR18 agonists reported to date.

Post assessment of true external set prediction capability, the MLR model was deployed to screen 12,449 DrugBank compounds, followed by a screening pipeline involving molecular docking, druglikeness, ADMET, protein-ligand stability assessment using deep learning algorithm, molecular dynamics, and molecular mechanics. The current findings strongly evidenced DB05790 as a potential lead for prospective interference of oxysterol-mediated GPR183 overexpression, warranting further in vitro and in vivo validation.

COMPLEMENT, HALLMARK_IL6_JAK_STAT3_SIGNALING, and HALLMARK_IL2_STAT5_SIGNALING pathways were activated, and all of these top 5 activated pathways were associated with immune regulation. GPR183 plays a prognostic factor in Acute Myeloid Leukemia by regulatingimmune regulation

Multiplex immunofluorescence and flow cytometry experiments in an additional cohort of 22 treatment-naïve and 30 IIIA/IIIB NSCLC patients treated with neoadjuvant chemoimmunotherapy verified these findings. Overall, our analysis revealed the functions of TIBs and their potential effect on clinical treatment in NSCLC.