Life Sciences & Biotechnology
Title : | Understanding the role of neutrophil heterogeneity and its therapeutic potential in the inflammatory liver disease Acute-on-Chronic Liver Failure (ACLF) |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Pragyan Acharya, All India Institute Of Medical Sciences (AIIMS), New Delhi |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | dr.pragyan.acharya@gmail.com |
Details
Executive Summary : | Acute-on-chronic liver failure (ACLF) is a condition where an injury occurs over underlying chronic liver disease, leading to rapid depletion of hepatic reserves and innate immune activation, resulting in systemic organ damage and mortality. Innate immune activation is a significant determinant of short-term mortality, with approximately 50% of patients dying within the first 28 days of diagnosis. Modulating innate immune responses is a promising therapeutic strategy in ACLF. Neutrophil-to-lymphocyte ratio (NLR) is another determinant of patient mortality in ACLF, indicating the importance of neutrophil expansion in its pathogenesis. ACLF patients also have neutrophil defects in phagocytosis and ROS production. Recently, heterogeneous neutrophil sub-populations in circulation of healthy and diseased individuals have been described, varying based on cell surface CD markers, density, or maturity. In inflammatory diseases, certain sub-populations are highly expanded, such as sepsis patients with a highly expanded OLFM4+ neutrophil population and CD177+ neutrophils in inflammatory bowel disease (IBD). Low-density neutrophils (LDN) are also highly expanded during many inflammatory diseases, contributing to the immune-pathogenesis of inflammatory diseases. Preliminary studies show the presence of pathogenic neutrophil sub-populations expressing high levels of CD177 surface marker and signatures of LDN, which are associated with 28-day mortality. This study aims to deep-proteomic and functional characterization of relevant neutrophil sub-populations in ACLF and identify therapeutic targets for immunomodulation. |
Co-PI: | Dr. Jayanth Kumar Palanichamy, All India Institute Of Medical Sciences (AIIMS), New Delhi-110029, Dr. Kalpana Luthra, All India Institute Of Medical Sciences (AIIMS), New Delhi-110029, Dr. Shalimar, All India Institute Of Medical Sciences (AIIMS), New Delhi-110029 |
Total Budget (INR): | 45,13,696 |
Organizations involved