Immune checkpoints are critical for maintaining autoimmune homeostasis and are implicated in various autoimmune diseases, with their significance increasingly recognized. Investigating the functions and mechanisms of these checkpoints is essential for the development of more effective treatments. Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4) stands out as a unique immune checkpoint, with limited expression in most normal tissues but prominent presence in various hematological and solid tumors. It is also expressed on numerous immune and stromal cells, functioning as both a "Tumor Immune Checkpoint" and a "Tumor Stromal Immune Checkpoint." Due to its distinct expression profile, LILRB4 plays a pivotal role in tumors, autoimmune diseases, allergic reactions, and the maintenance of immune homeostasis during transplantation and pregnancy. A thorough understanding of its ligands, functions, mechanisms, and ongoing therapeutic strategies targeting LILRB4 will be crucial for the development of advanced therapeutic options. This review examines LILRB4 expression and function across multiple diseases and discusses therapeutic approaches targeting LILRB4 in various contexts. Additionally, the potential of combining current drugs with LILRB4-targeted therapies is explored. Challenges in developing LILRB4-targeting drugs are also addressed, offering valuable insights for future research.
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http://dx.doi.org/10.1016/j.bcp.2025.116762 | DOI Listing |
JAMA Netw Open
January 2025
Department of Child and Adolescent Psychiatry-Psychotherapy, University Hospital Ulm, Ulm, Germany.
Importance: Associations between child maltreatment (CM) and health have been studied broadly, but most studies focus on multiplicity (number of experienced subtypes of CM). Studies assessing multiple CM characteristics are scarce, partly due to methodological challenges, and were mostly conducted in patient samples.
Objective: To determine the importance of CM characteristics in association with physical multimorbidity in adulthood for women and men in a German representative sample.
Proc Natl Acad Sci U S A
January 2025
Shenzhen Key Laboratory of Biomolecular Assembling and Regulation, Department of Neuroscience, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
Ankyrin Repeat Domain-containing Protein 11 () is a causative gene for KBG syndrome, a significant risk factor for Cornelia de Lange syndrome (CdLS), and a highly confident autism spectrum disorder gene. Mutations of lead to developmental abnormalities in multiple organs/tissues including the brain, craniofacial and skeletal bones, and tooth structures with unknown mechanism(s). Here, we find that ANKRD11, via a short peptide fragment in its N-terminal region, binds to the cohesin complex with a high affinity, implicating why mutation can cause CdLS.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Epstein-Barr virus (EBV) establishes persistent infection, causes infectious mononucleosis, is a major trigger for multiple sclerosis and contributes to multiple cancers. Yet, knowledge remains incomplete about how the virus remodels host B cells to support lytic replication. We previously identified that EBV lytic replication results in selective depletion of plasma membrane (PM) B cell receptor (BCR) complexes, composed of immunoglobulin and the CD79A and CD79B signaling chains.
View Article and Find Full Text PDFPharmacoecon Open
January 2025
HTA & Pharmaceutical Economics Department, Italian Medicines Agency (AIFA), Rome, Italy.
Background: The authorization of new therapeutic indications for drugs already reimbursed by the Italian National Health Service (NHS) represents a matter of importance. This study aims to estimate the additional discount attributed to the extension of indications (EoIs) to explore the potential correlation between spending and negotiated discounts and to find specific factors (determinants) that impact on discount.
Methods: The study focused on drugs approved in Italy between 2003 and 2017 with at least four therapeutic indications, including the first approved and EoIs, with follow-up extended until 2021 to acquire all the information on the negotiation process that has been completed.
J Endocrinol Invest
January 2025
Department of Internal Medicine, Maastricht University Medical Center, Maastricht, 6229ER, the Netherlands.
Purpose: Elevated methylglyoxal (MGO) levels and altered immune cell responses are observed in diabetes. MGO is thought to modulate immune cell activation. The current study investigated whether fasting or post-glucose-load plasma MGO concentrations are associated with circulating immune cell counts and activation in a large cohort study.
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