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eISSN 3022-7712

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Clin Transplant Res 2024; 38(4): 309-325

Published online December 31, 2024

https://doi.org/10.4285/ctr.24.0058

© The Korean Society for Transplantation

Targeting T helper 17 cells: emerging strategies for overcoming transplant rejection

Young Joon Lee1,2 , Mi-La Cho1,2

1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea 2Lab of Translational ImmunoMedicine (LaTIM), College of Medicine, The Catholic University of Korea, Seoul, Korea

Correspondence to: Mi-La Cho
Department of Pathology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
E-mail: iammila@catholic.ac.kr

Received: November 5, 2024; Revised: December 2, 2024; Accepted: December 2, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Solid organ transplantation has significantly improved the survival rate of patients with terminal organ failure. However, its success is often compromised by allograft rejection, a process in which T helper 17 (Th17) cells play a crucial role. These cells facilitate rejection by enhancing neutrophil infiltration into the graft and by activating endothelial cells and fibroblasts. Additionally, Th17 cells can trigger the activation of other T cell types, including Th1, Th2, and CD8+ T cells, further contributing to rejection. An imbalance between Th17 and regulatory T cells (Tregs) is known to promote rejection. To counteract this, immunosuppressive drugs have been developed to inhibit T cell activity and foster transplant tolerance. Another approach involves the adoptive transfer of regulatory cells, such as Tregs and myeloid-derived suppressor cells, to dampen T cell functions. This review primarily focuses on the roles of Th17 cells in rejection and their interactions with other T cell subsets. We also explore various strategies aimed at suppressing T cells to induce tolerance.

Keywords: Transplantation, Allograft rejection, Th17 cells, Immune tolerance

HIGHLIGHTS
  • T helper 17 (Th17) promotes allograft rejection and can also activate Th1, Th2, and CD8T cells.

  • Interleukin-17 promotes the maturation of dendritic cells, the activation of T cells, and the rejection of allografts.

  • Th17–regulatory T cell imbalance promotes allograft rejection.

  • Immunomodulatory drugs and cell-based therapy are under development to control Th17 cells and reduce the risk of transplantation rejection.