Asya Dolgikh, Samuel Rommelaere, Aseel Ghanem, Bianca Petrignani, Mickael Poidevin, Estee Kurant, Bruno Lemaitre
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引用次数: 0
Abstract
Efferocytosis, the efficient clearance of apoptotic cells (ACs) by phagocytes, is vital for maintaining tissue homeostasis. Here, we reveal the role of the secreted protein NimB1 in reducing apoptotic cell recognition and binding in the early stages of efferocytosis. NimB1 is expressed in macrophages (also called plasmatocytes) and binds to ACs in a phosphatidylserine-dependent manner. Structural analysis shows that NimB1 shares striking similarities with the bridging molecule NimB4, and possesses two phosphatidylserine-binding motifs, supporting its role in efferocytosis. Larval macrophages of NimB1-null Drosophila mutants display a hyper-phagocytic phenotype characterized by increased engulfment of ACs. Confocal imaging reveals that NimB1 specifically inhibits early steps in internalization of ACs, but does not impact phagosome maturation. We find that NimB1 is a secreted factor that negatively regulates efferocytosis, antagonizing the role of NimB4. Our study and the analogous opposing roles of Draper Isoforms II and I in efferocytosis suggest that a balance of negative and positive regulators allows optimization of the rate of apoptotic cell clearance by macrophages.
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Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community.
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To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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