The IL-23/IL-17 axis is the most important signaling pathway underlying psoriasis pathogenesis. Recent studies have identified mast cells, and not T cells, as main source of IL-17A in psoriasis, although their exact pathophysiologic role still remains to be determined. After therapy, psoriatic lesions resolve almost completely, but after treatment cessation, lesions most often reappear at the exact same body sites. In clinically resolved psoriasis, resident memory T cells (TRM) are a local cytokine source, which could steer the wheel toward a proinflammatory environment and disease recurrence. We hypothesize that IL-17A is stored in mast cells, waiting to be released to reactivate the inflammatory loop, and that TRM might drive/restart cytokine production and/or release in mast cells. Immunostaining of IL-17A, T cells (CD3), neutrophils (myeloperoxidase) and mast cells (tryptase) showed that in lesional psoriatic skin 83% of IL-17A+ cells were mast cells, while 14% were neutrophils and only 3% were T cells. In resolved lesions, IL-17A+ mast cell counts remained high, whereas all other IL-17A expressing cells had nearly vanished. Numbers of IL-17A+ mast cells at the follow-up timepoint (resolved lesion) correlated with PASI score at follow-up (spearman correlation, r=0.68, p value=0.0176), whereas T cell counts or IL-17A+ T cell counts showed no correlation. Immunostaining of TRM (CD103+), IL-17A and tryptase revealed that IL-17A+ mast cells reside in close proximity to TRM in both active and resolved psoriatic lesions. Our results demonstrate that IL-17A+ mast cells persist in clinically resolved lesional skin and could be indicative for early recurrence. Residing next to TRM, mast cell-derived IL-17A might be essential to restart the inflammatory feedback loop that leads to recurrence of psoriasis.

ESDR358 - IL-17A+ mast cells in resolved psoriasis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.