FTY720, an S1P receptor antagonist, significantly inhibits ER stress-induced IEC injury. Our findings highlight the pathogenic role of host SPHK1 in gastrointestinal injury during aGVHD and suggest that targeting SPHK1 could be a therapeutic strategy for managing this condition.

Molecular docking and dynamics simulations showed that R120P and F125S weaken binding affinity for natural agonist sphingosine-1-phosphate (S1P) and FTY720P, while antagonist W146 retained strong binding...Collectively, these findings identified high-risk nsSNPs in S1PR1 gene with potential structural and functional implications, particularly in diseases involving impaired receptor signaling. These findings enhanced our understanding of how specific nsSNPs can influence disease susceptibility, drug response, and receptor function, paving the way for precision medicine approaches in treating autoimmune and inflammatory disorders.

P2, N=15, Enrolling by invitation, Viatris Pharmaceuticals Co., Ltd. | Not yet recruiting --> Enrolling by invitation

P1, N=6, Active, not recruiting, Viatris Innovation GmbH | Not yet recruiting --> Active, not recruiting

P1, N=6, Not yet recruiting, Viatris Innovation GmbH

Depleting CD4+ T-cells, or blocking lymphocyte egress from the lymph nodes with FTY720, rescues tumor growth in mice with conditional deletion of Dnmt1 in ECs (Dnmt1iECKO) and dramatically shortens overall survival, whereas NK cells are dispensable...Finally, immune checkpoint blockade (ICB) administered to Dnmt1iECKO mice with experimental melanoma lung metastasis reduces tumor burden, with some mice showing tumor eradication. Our findings identify endothelial Dnmt1 as a key regulator of vascular-mediated anti-tumor immunity, providing a rationale for integrating epigenetic modulation of the vasculature with cancer immunotherapy regimens.

P=N/A, N=134, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Jul 2025 | Trial primary completion date: Jun 2026 --> Jul 2025

P2, N=15, Not yet recruiting, Viatris Pharmaceuticals Co., Ltd.

Our findings indicate that antigen-specific therapy with PS liposomes mimicking apoptotic bodies downregulates the MOG-specific inflammatory immune response and expands Breg and Treg cells, offering a safe, versatile, and easily applicable approach that strongly supports its potential for near-future clinical translation in MS.

This study demonstrates that adjuvants can facilitate recruitment of cDC1s to the peritoneal cavity, a feature that may contribute to the effectiveness of i.p. administration on elicitation of CD8 T cell responses. Furthermore, we demonstrate that CAF09b-induced CD8 T cell responses require BATF3-dependent cDC1 cells. Understanding cDC1 and CD8 T cell dynamics via different immunization routes may aid in the design of more effective vaccine strategies.

Mice with EC-specifically MYPT1-deficient (Mypt1ΔEC) also showed coronary endothelial hyperpermeability, and treatment with the S1PR1 agonist FTY720 failed in alleviating the pathological effects. At 1 month post-transverse aortic constriction, both Mypt1ΔEC and S1pr1ΔEC mice displayed aggravated pathological cardiac remodeling. These findings suggest that the S1PR1-MYPT1 signaling is crucial for coronary endothelial permeability and myocardial microenvironmental homeostasis under pressure overload, targeting which may offer therapeutic potential for related heart diseases.