National Heart, Lung, and Blood Institute 1R01HL184013-01

B-1a Cells and Acute Inflammation

NIH grant awarded to Feinstein Institute for Medical Research to study B-1a cells' role in Acute Lung Injury and develop therapeutic strategies using Compound 11 to prevent cell depletion and reduce ALI severity.

Description

This project investigates the role of B-1a cells in mitigating Acute Lung Injury (ALI), a life-threatening condition often caused by sepsis or ischemia-reperfusion injury. The research aims to understand how depletion of B-1a cells contributes to ALI through inflammatory dysregulation and to develop therapeutic strategies to prevent this depletion. Key findings include the discovery of a novel interaction between Siglec-G and CD47 on B-1a cells, which disrupts the "don't-eat-me" signaling pathway, leading to B-1a cell trogocytosis by neutrophils. The project proposes using Compound 11 (C11), an 11-amino acid oligopeptide derived from CD47, to inhibit this interaction and restore B-1a cell function. The research will elucidate molecular mechanisms by which Siglec-G disrupts CD47 signaling, investigate how B-1a cells promote lung endothelial cell survival, and evaluate the therapeutic potential of C11 in preclinical models.

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