The Plasticity of Th17 Cells in the Pathogenesis of Rheumatoid Arthritis

Abstract

Helper T (Th) cells play an important role in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). It has been revealed that Th17 cells can shift to Th1 cells (i.e., "nonclassic Th1 cells"), which are reported to be more pathogenic than Th17 cells per se. Thus, the association of Th cells in the pathogenesis of autoimmune disease has become more complicated. We recently reported using peripheral blood from untreated and early-onset RA patients that the ratio of CD161+Th1 cells (i.e., Th17-derived Th1 cells to CD161+Th17 cells) is elevated and that levels of interferon-γ (IFNγ)+Th17 cells are inversely correlated with levels of anti-CCP antibodies. Here, we review the plasticity of Th17 cells in the pathogenesis of RA, suggesting possible implications for novel therapies.

Keywords: CD161; Th17; classic Th1; nonclassic Th1; plasticity; rheumatoid arthritis.

Figure 1

The role of Th17 cells in the pathogenesis of rheumatoid arthritis (RA). Th17 cells play a central role in the pathogenesis: (a) IL-17 stimulates synovial fibroblasts to produce IL-6 [5] and (b) macrophages to produce TNFα [6]; (c) IL-17 also stimulates osteoblasts to produce RANKL, potently inducing osteoclastogenesis [2,3]; (d) In addition, IL-17 induces osteoclastogenesis from monocytes alone in the absence of osteoblasts or RANKL [7]; (e) RANKL and TNFα synergistically induce osteoclastogenesis [7]; (f) IL-6 induces differentiation of Th17 cells [8]; (g) TNFα is produced by Th17 cells per se; thus, Th17 cells differentiate to nonclassic Th1 in an autocrine or paracrine manner [9]; (h) RANKL expressed on the surface of Th17 cells converts nonresorptive osteoclasts to resorptive osteoclasts via cell–cell contact [10]. RANKL, receptor activator of nuclear factor ĸB.