Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2019; 25(25): 3123-3135
Published online Jul 7, 2019. doi: 10.3748/wjg.v25.i25.3123
Revisiting the liver’s role in transplant alloimmunity
Nitin Abrol, Caroline C Jadlowiec, Timucin Taner
Nitin Abrol, Timucin Taner, William J. von Liebig Center for Transplantation and Clinical Regeneration, Massyo Clinic, Rochester, MN 55905, United States
Caroline C Jadlowiec, Transplant Center, Mayo Clinic, Phoenix, AZ 85259, United States
Author contributions: Abrol N, Jadlowiec CC and Taner T participated in the literature search and drafting of the manuscript.
Conflict-of-interest statement: No conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Timucin Taner, FACS, MD, PhD, Associate Professor, Surgeon, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, United States.
Telephone: +1-507-266-3841 Fax: +1-507-266-9806
Received: March 15, 2019
Peer-review started: March 15, 2019
First decision: April 11, 2019
Revised: April 25, 2019
Accepted: May 18, 2019
Article in press: May 18, 2019
Published online: July 7, 2019

The transplanted liver can modulate the recipient immune system to induce tolerance after transplantation. This phenomenon was observed nearly five decades ago. Subsequently, the liver’s role in multivisceral transplantation was recognized, as it has a protective role in preventing rejection of simultaneously transplanted solid organs such as kidney and heart. The liver has a unique architecture and is home to many cells involved in immunity and inflammation. After transplantation, these cells migrate from the liver into the recipient. Early studies identified chimerism as an important mechanism by which the liver modulates the human immune system. Recent studies on human T-cell subtypes, cytokine expression, and gene expression in the allograft have expanded our knowledge on the potential mechanisms underlying immunomodulation. In this article, we discuss the privileged state of liver transplantation compared to other solid organ transplantation, the liver allograft’s role in multivisceral transplantation, various cells in the liver involved in immune responses, and the potential mechanisms underlying immunomodulation of host alloresponses.

Keywords: Liver transplantation, Alloimmunity, Liver-kidney transplant, Tolerance, Rejection

Core tip: The liver not only protects itself from host alloimmune responses, but also modulates alloimmune responses to other simultaneously transplanted solid organs like heart or kidney. The titer of donor specific alloantibodies decreases after liver transplantation, making transplantation of other solid organs possible even in highly sensitized high-risk patients. The immune cells from the liver allograft cross-talk with recipient immune cells and modulate the immune system towards tolerance. The cross-talk between these cells suppress the genes involved in alloimmunity and upregulate the genes involved in tissue repair and metabolism.