The Biological Basis of Disease Recurrence in Psoriasis

A Historical Perspective and Current Models

Lluís Puig; Antonio Costanzo; Ernesto J. Muñoz-Elías; Maria Jazra; Sven Wegner; Carle F. Paul; Curdin Conrad

Disclosures

The British Journal of Dermatology. 2022;186(5):773-781. 

In This Article

Conclusions and Unresolved Questions

The current model of psoriasis immunopathogenesis is presented in Figure 1. Following keratinocyte damage, IL-23 plays a major role in the activation of Th17; clonal expansion and differentiation of these cells stimulates the production of proinflammatory cytokines, leading to keratinocyte hyperproliferation and a feedforward inflammatory response. The model incorporates an IL-17 positive feedback loop, in which Th17-derived IL-17 induces overproduction of IL-17 from psoriatic keratinocytes, which in turn induces Th17 cells to secrete more IL-17.[90,91]

IL-17-producing T cells, epidermal-resident LCs and TRM cells all play an important role in the pathogenesis of psoriasis and the recurrence of disease in resolved psoriatic lesions. A 'residual disease genomic profile' exists in resolved lesions, characterized by the elevated expression of proinflammatory genes, including those encoding IL-12, MX1, IL-22, IL-17 and IFN-γ. IL-17-producing CD8+ TRM cells have been found in clinically resolved lesions, suggesting that TRM cells represent a nidus of latent inflammation that can predispose to reactivation of overt inflammation and lesion recurrence. Therefore, novel treatments for psoriasis that aim at sustained disease remission[92] should target the depletion of pathogenic CD8+ TRM cells.

The clinical efficacy of IL-23 and IL-17 antagonists in the treatment of psoriasis underscores the critical role of these cytokines and their cellular targets in the pathogenesis of this disease. TRM cells initiate and perpetuate immune responses, play an important role in lesion recurrence and may be differentially regulated by IL-23 and IL-17 antagonism. Further studies investigating the effect of approved IL-23 and IL-17 antagonists on lesion recurrence and long-term disease control are warranted.

processing....