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Role of Complement Activation in Allograft Inflammation

  • Nicholas H. Chun
  • Julian K. Horwitz
  • Peter S. HeegerEmail author
Immunology (R Fairchild, Section Editor)
  • 30 Downloads
Part of the following topical collections:
  1. Topical Collection on Immunology

Abstract

Purpose of Review

Novel paradigms have broadened our understanding of mechanisms through which complement mediates allograft inflammation/injury. Herein, we review advances in the field and highlight therapeutic implications.

Recent Findings

Pre-clinical and translational human trials have elucidated complement-dependent mechanisms of post-transplant ischemia-reperfusion (I/R) injury. Immune cell-derived, and intracellular, complement activation is newly linked to proinflammatory T cell immunity relevant to allograft rejection. Complement-induced immune regulation, including C5a ligation of C5a receptor 2 on T cells, C5a/C5a receptor 1 interactions on regulatory myeloid cells, and C1q binding to CD8+ T cells, can inhibit proinflammatory T cells and/or prolong murine allograft survival. Pilot trials of complement inhibition to treat/prevent human I/R- or antibody-initiated allograft injury show promise.

Summary

The complement system participates in allograft injury through multiple context-dependent mechanisms involving various components and receptors. These new insights along with development and implementation of individualized complement inhibitory strategies have potential to improve transplant outcomes.

Keywords

Complement T cell activation Ischemia reperfusion injury Allograft inflammation Antibody-mediated rejection 

Notes

Funding

The work was supported by NIH grants R01 AI071185 and AI132405 awarded to PSH and K08 AI135101 to NC.

Compliance with Ethical Standards

Conflict of Interest

Peter Heeger reports grants from Alexion and serves on the Chemocentryx scientific advisory board. Nicholas Chun reports grants from NIAID during the conduct of the study. Julian Horwitz declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Nicholas H. Chun
    • 1
    • 2
  • Julian K. Horwitz
    • 1
    • 3
  • Peter S. Heeger
    • 1
    • 2
    • 3
    Email author
  1. 1.Translational Transplant Research Center, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Division of Nephrology in the Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.The Precision Institute of ImmunologyIcahn School of Medicine at Mount SinaiNew YorkUSA

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