Histidine-rich glycoprotein in necrotic cell/pathogen clearance and autoimmunity
Histidine-rich glycoprotein (HRG) is an abundant multi-functional plasma protein of vertebrates. We have shown HRG is a novel pattern recognition molecule that forms an adaptor complex with other innate immunity molecules to mediate the clearance of necrotic cells through phagocytes. Based on these observations we propose that HRG plays a key role in maintaining efficient clearance of necrotic cells from the circulation, a critical process of the innate immune system for the elimination of self-antigens to prevent autoimmune disease. In addition, we have observed striking similarities between the recognition of necrotic cells and pathogens by the innate immune system. We propose that the same molecular mechanisms are used to clear these potentially harmful materials and promote the resolution of tissue injury (Priebatsch et al., 2017, Patel et al., 2013, Poon et al., 2011 ).
We are currently working on:
(1) Defining the in vivo role of HRG in necrotic cell clearance using HRG deficient mice.
(2) Investigating the role of HRG in pathogen recognition and clearance.
(3) Defining the HRG complex for the recognition of necrotic cells and pathogens.