Natural killer (NK) cells, in addition to their cytotoxicity function, harbor prominent cytokine production capabilities and contribute to regulating autoimmune responses. T-cell immunoglobulin and mucin domain containing protein-3 (Tim-3) is one of the inhibitory receptors on NK cells and a promising immune checkpoint target. We recently found that phosphatidylserine (PS) binding to Tim-3 can suppress NK cell activation. Therefore, based on the therapeutic potential of Tim-3 in NK-cell-mediated diseases, we developed a photoswitchable ligand of Tim-3, termed photophosphatidylserine (), that mimics the effects of PS. Upon 365 or 455 nm light irradiation, the isomer of cyclically conversed the cis/trans configuration, resulting in an active/inactive Tim-3 ligand, thus modulating the function of NK cells and . We also demonstrated that reversible enabled optical control of acute hepatitis. Together, phoPS may be an appealing tool for autoimmune diseases and cytokine storms in the future.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jacs.1c11498 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Trying to Kill a Killer; Impressive Killing of Patient Derived Glioblastoma Cultures Using NK-92 Natural Killer Cells Reveals Both Sensitive and Highly Resistant Glioblastoma Cells.
Cells
January 2025
Department of Molecular Medicine and Pathology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
The overall goal of this work was to assess the ability of Natural Killer cells to kill cultures of patient-derived glioblastoma cells. Herein we report impressive levels of NK-92 mediated killing of various patient-derived glioblastoma cultures observed at ET (effector: target) ratios of 5:1 and 1:1. This enabled direct comparison of the degree of glioblastoma cell loss across a broader range of glioblastoma cultures.
View Article and Find Full Text PDFFlow Cytometric Assessment of FcγRIIIa-V158F Polymorphisms and NK Cell Mediated ADCC Revealed Reduced NK Cell Functionality in Colorectal Cancer Patients.
Cells
December 2024
BIH Center for Regenerative Therapies (BCRT), Therapy-Induced Remodeling in Immuno-Oncology, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions.
View Article and Find Full Text PDFDecoupling Individual Host Response and Immune Cell Engager Cytotoxic Potency.
ACS Nano
January 2025
Aix-Marseille Univ., CNRS, INSERM, LAI, Centuri Living Systems, 13009 Marseille, France.
Immune cell engagers are molecular agents, usually antibody-based constructs, engineered to recruit immune cells against cancer cells and kill them. They are versatile and powerful tools for cancer immunotherapy. Despite the multiplication of engagers tested and accepted in the clinic, how molecular and cellular parameters influence their actions is poorly understood.
View Article and Find Full Text PDFPrognostic Impact of Aetiology in Adult Hemophagocytic Lymphohistiocytosis: Insights from an Intensive Care Unit Experience.
Eur J Case Rep Intern Med
December 2024
Intensive Care Unit, Pedro Hispano Hospital, Matosinhos Local Health Unit, Matosinhos, Portugal.
Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome marked by excessive immune activation. It can be triggered by various factors, including infections, malignancies, and autoimmune diseases, making the diagnosis challenging due to its overlap with other severe conditions.
Case Reports: We discuss two intensive care unit (ICU) cases illustrating the diverse manifestations of HLH and the critical importance of early recognition and treatment.
Hemophagocytic Lymphohistiocytosis Due to Ehrlichiosis: A Case Series.
HCA Healthc J Med
December 2024
Research Medical Center, Kansas City, MO.
Background: Hemophagocytic lymphohistiocytosis (HLH) is an immunologic syndrome characterized by excessive inflammation and tissue injury due to uncontrolled activation of the phagocytic system. The underlying mechanism is a lack of downregulation of activated macrophages and lymphocytes by natural killer and T cells. Unfortunately, the diagnosis is often delayed or missed due to the rarity of the disease, decreased awareness, and clinical picture variability.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!