Editors' ChoiceAutoimmunity

Lurking culprits

See allHide authors and affiliations

Science Translational Medicine  11 Oct 2017:
Vol. 9, Issue 411, eaap8167
DOI: 10.1126/scitranslmed.aap8167

Abstract

IL-17–producing T cells persist in resolved psoriatic skin lesions.

Biologic disease-modifying antirheumatic drugs (DMARDs) have revolutionized the treatment of psoriasis and psoriatic arthritis. Among these new therapeutic agents are monoclonal antibodies targeting tumor necrosis factor–α, interleukin-12 p40 (IL-12 p40), and IL-17A. As with other rheumatologic diseases, the response of patients to targeted therapies has helped to define mechanisms of disease pathogenesis. For example, the effectiveness of anti–IL-17A monoclonal antibody demonstrates the pathogenicity of IL-17A, at least in the subset of patients who respond to this particular therapy. Interestingly, when therapy is stopped, psoriatic skin lesions tend to recur in the very same locations.

In a recent article from The Journal of Clinical Investigation, Matos et al. hypothesized that psoriasis-specific T cells residing in the skin may explain why psoriatic skin lesions tend to recur in the same locations. The authors found oligoclonal populations of T cells producing IL-17A in resolved and active psoriatic skin lesions, and they also identified putative pathogenic clones, with the vast majority of T cells in psoriatic skin lesions identified as αβ T cells and only a small minority (~1%) as γδ T cells. The authors concluded that these cells are likely to be disease-initiating pathogenic T cells in psoriasis, but further study is required to demonstrate this definitively.

A major implication of Matos et al. is the notion that a lasting cure might be attainable if skin-resident, pathogenic T cells could be eliminated, but numerous other compelling questions still remain. For example, patients with psoriasis also frequently suffer from inflammatory arthritis and eye disease (e.g., uveitis), and it isn’t uncommon for patients to repeatedly experience flares involving the very same joints or the very same eye. Future studies are likely to test whether similar T cell clones also lurk in other tissues that are vulnerable to recurrent inflammation and whether the same pathogenic T cell clones are found in a variety of affected tissues.

Highlighted Article

View Abstract

Navigate This Article