Clinical significance of Th17 cells in kidney transplantation

Abstract

Transplantation research has focused on cytotoxic T-cell and plasma cell/B-cell-targeted strategies, but little attention has been paid to the role of T helper 17 (Th17) cells in allograft dysfunction. However, accumulating evidence suggests that Th17 cells contribute to the development of acute and chronic allograft injury after transplantation of various organs, including the kidney. This review summarizes recent reports on the role of Th17 cells in kidney transplantation. Means of improving allograft outcomes by targeting the Th17 pathway are also suggested.

Keywords: Allograft rejection; Chronic allograft dysfunction; Kidney transplantation; Mammalian target of rapamycin; Th17 cells.

Figure 1.

Differentiation of T helper 17 (Th17) cells in mice and humans and the functions of Th17 cytokines and chemokines. Th17 cells secrete interleukin 17A/F (IL-17A/F), interleukin 22 (IL-22), interleukin 21 (IL-21), and C-C motif chemokine ligand 20 (CCL20), which modulate inflammation and immune cell recruitment. TGF-β, Transforming growth factor β; STAT3, signal transducer and activator of transcription 3; RORγt, RAR-related orphan receptor γt; CCR, C-C motif chemokine receptor; ACT1, actin 1; TRAP6, thrombin receptor-activating peptide-6; NF-κB, nuclear factor κB; MAPK, mitogen-activated protein kinase; IgG, immunoglobulin G.

Figure 2.

Activation of the T helper 17 (Th17) pathway in kidney transplantation recipients with chronic allograft dysfunction (CAD). The proportion of Th17 cells (interleukin 17⁺ [IL-17⁺]/cluster of differentiation 4⁺ [CD4⁺]); the IL-1β, receptor for advanced glycation end products (RAGE), and high mobility group box 1 (HMGB-1) messenger RNA (mRNA) levels; and the IL17, interleukin 33 (IL-33), and RAGE levels in peripheral blood are higher in patients with CAD. Modified from Chung et al. [41]. LTS, long-term stable; ES, early stable; ESRD, end stage renal disease; HC, healthy control; PCR, polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay. ^ap < 0.05 for each comparison.

Figure 3.

Effec inhibitors on the mTOR/signal transducer and activator of transcription 3 (STAT3) signaling pathway in T helper 17 (Th17) cells. PI3K, phosphoinositide 3-kinase; S6K1, ribosomal protein S6 kinase beta-1.