emerging evidence for critical involvement of the interleukin‐17 pathway in both psoriasis and psoriatic arthritis

O FitzGerald, R Winchester - Arthritis & rheumatology, 2014 - Wiley Online Library
O FitzGerald, R Winchester
Arthritis & rheumatology, 2014Wiley Online Library
Menon and colleagues, in this issue of Arthritis & Rheumatology, show that in both
rheumatoid arthritis (RA) and psoriatic arthritis (PsA), inflammatory T cells committed to the
synthesis of interleukin-17 (IL-17)–positive Th17 T cells are considerably enriched in the
patients' synovial fluid relative to the peripheral blood (1). Both RA and PsA were previously
considered to be Th1-mediated diseases; however, the prior identification of the Th17 cell
subset in RA has substantially changed the general concepts regarding the mechanisms of …
Menon and colleagues, in this issue of Arthritis & Rheumatology, show that in both rheumatoid arthritis (RA) and psoriatic arthritis (PsA), inflammatory T cells committed to the synthesis of interleukin-17 (IL-17)–positive Th17 T cells are considerably enriched in the patients’ synovial fluid relative to the peripheral blood (1). Both RA and PsA were previously considered to be Th1-mediated diseases; however, the prior identification of the Th17 cell subset in RA has substantially changed the general concepts regarding the mechanisms of mediation of autoimmune inflammation (2). The secretion of IL-17 by Th17 cells, which is up-regulated by IL-23 and IL-21, establishes an inflammatory pathway that results in joint inflammation and injury, mediated directly by this proinflammatory cytokine and indirectly by its induction of the production of IL-1 and tumor necrosis factor(TNF). The identification of the enhanced production of IL-17 further supports the rationale for new targets of therapy in PsA. Importantly, the study by Menon and colleagues showed that, first, these 2 diseases differ in terms of T cell phenotype. In patients with PsA, the T cell lineage producing IL-17 was predominantly CD8, whereas in patients with RA, the IL-17–producing T cells were present in only the CD4 lineage. This difference in T cell lineage and, presumably, in the driving peptide likely accounts for the clinical features, such as reactive new bone formation and axial involvement, that distinguish PsA from RA. Second, these authors found that the increase in the frequency of CD8 T cells elaborating IL-17 correlated with markers of inflammation and erosion in the aspirated PsA joint, suggesting that these cells contribute to the synovitis found in both RA and PsA. Third, these authors observed that, despite the overall correlations, there was considerable heterogeneity in the degree of IL-17 production in the joint fluid among patients with PsA, a finding that will be discussed in more detail below.
A considerable body of prior work provides a likely explanation for the difference observed in the current study by Menon et al between RA and PsA in the predominant T cell lineage that contains the pathogenic Th17 lymphocytes. Susceptibility to RA is well known to be associated with a number of different class II major histocompatibility complex (MHC) alleles of
Wiley Online Library