C1q as a potential tolerogenic therapeutic in transplantation

In 1963, Lepow and colleagues resolved C1, the first component of the classical pathway, into three components, which they named C1q, C1r, and C1s. All three of these components were demonstrated to be involved in causing hemolysis in vitro. For over 30 years after that seminal discovery, the primar...

Full description

Saved in:
Bibliographic Details
Published in:American journal of transplantation 2021-11, Vol.21 (11), p.3519-3523
Main Authors: Baldwin, William M., Valujskikh, Anna, Fairchild, Robert L.
Format: Article
Language:English
Subjects:
antigen presentation/recognition
Antigen-presenting cells
Apoptosis
autoimmunity
Cell death
cell death: apoptosis
Classical pathway
Complement Activation
complement biology
Complement C1q
Complement C1r
Complement C1s
Complement component C1q
editorial/personal viewpoint
Extracellular vesicles
Immune clearance
Immune response
immunosuppression/immune modulation
innate immunity
Macrophages
Pattern recognition receptors
Transplantation
Transplants & implants
Vesicles
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In 1963, Lepow and colleagues resolved C1, the first component of the classical pathway, into three components, which they named C1q, C1r, and C1s. All three of these components were demonstrated to be involved in causing hemolysis in vitro. For over 30 years after that seminal discovery, the primary function attributed to C1q was as part of the C1 complex that initiated the classical pathway of the complement cascade. Then, a series of papers reported that isolated C1q could bind to apoptotic cells and facilitate their clearance by macrophages. Since then, rheumatologists have recognized that C1q is an important pattern recognition receptor (PRR) that diverts autoantigen containing extracellular vesicles from immune recognition. This critical function of C1q as a regulator of immune recognition has been largely overlooked in transplantation. Now that extracellular vesicles released from transplants have been identified as a major agent of immune recognition, it is logical to consider the potential impact of C1q on modulating the delivery of allogeneic extracellular vesicles to antigen presenting cells. This concept has clinical implications in the possible use of C1q or a derivative as a biological therapeutic to down‐modulate immune responses to transplants. The authors review the evidence that the complement component C1q is a pattern recognition receptor and propose that C1q modulates the immune response to transplants by altering the delivery of allogeneic extracellular vesicles to antigen presenting cells.
ISSN:1600-6135
1600-6143
DOI:10.1111/ajt.16705