Imiquimod (IMQ), a TLR 7/8 agonist, was shown to induce a self-limited Th17-dominated contact dermatitis in healthy skin, but not the full picture of psoriasis. Whilst such an innate “first strike” of IMQ is needed for inducing inflammation, a “second strike” might perpetuate inflammation and induce the characteristic phenotype of psoriatic plaques. Here, IMQ was tested on clinically healed plaques of 5 psoriasis patients for inducing a “second strike”, namely the activation of CD103+ tissue-resident memory T cells (TRM) that recognize specific cutaneous antigens and thereby maintain the inflammatory response in the skin. Former psoriatic lesion (FL) and never-affected area as control (NL) were treated with IMQ 5% cream, 0.2 g/cm2, twice a week for 4 weeks. Skin biopsies (n=2) were collected at baseline and day 28 from each site and processed for histology, FACS and bulk RNA-seq analysis. Only 1 patient showed the full clinical and histological picture of psoriasis in activated FL. Results were also confirmed by transcriptome analysis using an existing dataset on psoriasis. Moreover, an increased number of CD4+CD103+KI67+ cells was detected in the skin of this patient compared to the others. Interestingly, preliminary data hints at triggering of T cell proliferation by autoantigens from the skin in this patient. We validated for the first time a “two-strike” model for psoriasis, potentially leading to “treat hard and early” concepts to avoid the accumulation of TRM in the skin and thus prevent relapse-remitting affection of the same sites.
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© 2022 Published by Elsevier Inc.
