公开(公告)号：US20190282616A1

公开(公告)日：2019-09-19

申请号：US16347752

申请日：2017-11-03

Applicant: University of Virginia Patent Foundation

Inventor： Kodimangalam S. Ravichandran ,  Claudia Zhuyun Han

IPC: A61K35/12 ,  A61K38/20 ,  C07K14/52 ,  C07K14/65 ,  G01N33/68 ,  A61K38/17 ,  A61K9/127

Abstract: Professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis. Since these phagocytes reside in proximity in most tissues, whether cross-communication exists between them during cell clearance, and how this might impact inflammation are not known. Here, we show that macrophages, via the release of a soluble growth factor and microvesicles, redirect the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During apoptotic cell engulfment or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was dampened while engulfment of microvesicles was enhanced. Macrophages were refractory to this IGF-1 mediated engulfment modulation. Macrophages also released microvesicles, whose uptake by epithelial cells, enhanced by IGF-1, led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal a novel IGF-1 and microvesicle-dependent communication between macrophages and epithelial cells that can critically influence the magnitude of tissue inflammation in vivo.

公开(公告)号：US20230172877A1

公开(公告)日：2023-06-08

申请号：US17910613

申请日：2021-03-11

Applicant: University of Virginia Patent Foundation

Inventor： Kodimangalam S. Ravichandran ,  Christopher B. Medina

IPC: A61K31/132 ,  A61K31/661 ,  A61P29/00

CPC classification number: A61K31/132 ,  A61K31/661 ,  A61P29/00

Abstract: Disclosed aspects include characterizing of the metabolite secretome of apoptotic cells, deciphering metabolite-based communication between dying cells and neighboring live cells, and harnessing components of the secretome for beneficial effects in vivo. In representative embodiments, a composition comprising, consisting essentially of, or consisting of an effective amount of a plurality of metabolite compounds derived from an apoptotic cell is disclosed, as are methods of treating an inflammatory condition in a subject and modulating gene expression in a subject using the composition.

公开(公告)号：US20220381790A1

公开(公告)日：2022-12-01

申请号：US17429745

申请日：2020-02-11

Applicant: University of Virginia Patent Foundation

Inventor： Jeffrey J. Lysiak ,  Kodimangalam S. Ravichandran

IPC: G01N33/68 ,  C12N5/071

Abstract: The presently disclosed subject matter relates to compositions and methods useful for assessing fertilization competency in male and female gametes. In some embodiments, methods, kits, and compositions for identifying, selecting, and functionally evaluating fertilization competent sperm cells are provided, wherein the methods, kits, and compositions employ a reagent that selectively binds phosphatidylserine (PS).