<p dir="ltr">Neutrophils are critical for innate immunity, acting as the body's first line of defense. They are terminally differentiated and are short-lived white blood cells. Cyclin-dependent kinases (CDKs), traditionally associated with cell cycle progression are now known to regulate crucial neutrophil functions: CDK2 influences neutrophil migration, CDK4 and 6 regulate neutrophil extracellular traps (NETs) formation, CDK5 controls degranulation, and CDK7 and 9 are pivotal for apoptosis and inflammation resolution.</p><p dir="ltr">Despite extensive studies on CDK2 in cell cycle regulation, its role in neutrophil function remained uncharacterized until recently. Inhibiting CDK2 kinase activity significantly impairs neutrophil migration. Using phosphoproteomic methods, we identified key proteins in multiple cellular pathways affected by CDK2 inhibition, with Cyclin D3 emerging as a binding partner. Direct substrates of CDK2, including RCSD1, CCDC6, LMNB1, and STK10, were found to be essential for neutrophil motility. These findings provide insights into the molecular mechanisms underlying this process. Consequently, targeting CDK2 or its substrates presents potential therapeutic strategies for conditions involving aberrant neutrophil migration or neutrophil-mediated inflammation, offering new avenues for treating neutrophil-dominant inflammatory diseases and advancing our understanding of neutrophil regulation.</p><p dir="ltr">Emergency granulopoiesis, a response to severe inflammation, involves the increased production of neutrophils in hematopoietic tissue. Understanding the body's response to severe inflammation necessitates more precise and less invasive methods to track neutrophil development. To distinguish newly formed neutrophils from existing ones in the occurrence of emergency granulopoiesis, we developed a transgenic zebrafish line expressing a time-dependent GFP-RFP switch fluorescent protein, enabling quantification through simple GFP/RFP ratiometric imaging. This method bypasses the limitations of traditional photo-labeling, which requires strong laser lines and label subsets of existing neutrophils.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/26339011 |
| Date | 19 July 2024 |
| Creators | Ramizah Syahirah B Mohd Sabri (19180162) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/thesis/_b_Insights_into_cyclin-dependent_kinases_and_their_roles_in_neutrophil_dynamics_b_/26339011 |
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