Investigation of neutrophil’s unique polymorphic nucleus for its immunological relevance in inflammation and infection

• Applicant: Professor Dr. Tim Lämmermann, Ph.D.
• Subject Area: Immunology ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 551210984

Neutrophils are essential components of our innate immune system, playing a vital role in eliminating bacteria and fungi. Consequently, low levels of neutrophils can increase susceptibility to infections. Unlike most mammalian cells, which have spherical nuclei, neutrophils feature distinctively segmented nuclei. This characteristic feature of neutrophils has remained enigmatic for decades and continues to be a subject of great interest in immunology and cell biology. Despite years of study, the specific physiological implications of this unusual nuclear shape in neutrophil biology and its influence on immune responses remain largely unexplored. The polymorphic nature of neutrophil nuclei is closely associated with the function of the lamin B receptor (LBR), a critical component of the nuclear envelope that maintains nuclear structural integrity and organizes chromatin. This research proposal seeks to examine the physiological importance of the LBR-controlled polymorphic nuclear shapes in the development of neutrophils and their immune responses to both sterile inflammation and bacterial infections. Our study will focus on mice with a neutrophil-specific depletion of LBR, aiming to thoroughly investigate (1) the development and maturation of primary neutrophils in the absence of LBR protein, (2) the migration and response of LBR-deficient neutrophils to inflammatory stimuli and bacterial infections within tissues, (3) the impact of LBR-mediated polymorphic nuclei on neutrophil effector functions and overall immune responses. This research will deepen our understanding of neutrophil biology and potentially uncover new insights into their role in immune defense mechanisms.

• DFG Programme: Research Grants
• International Connection: South Korea
• Cooperation Partner: Professor Young-Min Hyun, Ph.D.