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Updated: Nov 4, 2025
In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
C1q as a potential tolerogenic therapeutic in transplantation
William M Baldwin1, Anna Valujskikh1, Robert L Fairchild1
1Inflammation and Immunity, Lerner Research Institute, Cleveland, Ohio, USA.
Insights
Complement component C1q, initially known for initiating the classical complement pathway, also binds apoptotic cells. This pattern recognition receptor may regulate immune responses in transplantation by interacting with extracellular vesicles.
Area of Science:
- Immunology
- Complement System
- Transplantation Immunology
Background:
- The complement component C1q was initially identified as part of the C1 complex initiating the classical complement pathway.
- Over time, C1q's role expanded to include binding apoptotic cells and facilitating their clearance by macrophages.
- Rheumatologists recognize C1q as a pattern recognition receptor (PRR) involved in immune tolerance by managing autoantigen-containing extracellular vesicles.
Purpose of the Study:
- To explore the overlooked function of C1q in transplantation immunology.
- To investigate the potential impact of C1q on the immune recognition of allogeneic extracellular vesicles in transplants.
- To consider C1q as a potential therapeutic agent for modulating transplant-related immune responses.
Main Methods:
- Review of existing literature on C1q function.
- Analysis of the role of extracellular vesicles in transplant rejection.
- Conceptual framework development linking C1q, extracellular vesicles, and transplant immunity.
Main Results:
- C1q's function as a regulator of immune recognition, particularly with extracellular vesicles, has been underappreciated in transplantation.
- Extracellular vesicles from transplants are now recognized as key players in immune recognition.
- C1q has the potential to modulate the interaction between allogeneic extracellular vesicles and antigen-presenting cells.
Conclusions:
- C1q's role in managing extracellular vesicles suggests a significant, yet largely unexplored, impact on transplantation.
- Targeting C1q could offer a novel therapeutic strategy to dampen immune responses against transplanted organs.
- Further research into C1q's interaction with allogeneic extracellular vesicles is warranted for clinical applications in transplantation.
Abstract:
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.
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