Dermatologists' appreciation of the central role that the interleukin (IL)-23/Th17 pathway plays in psoriasis has developed gradually, through research and serendipity, according to James Krueger, M.D., Ph.D., who spoke on the topic at the MauiDerm 2017 meeting.
"When I started researching psoriasis in the early 1990s, there was considerable debate about pathogenesis. But the dominant hypothesis was that keratinocytes were growing autonomously by overproduction of growth factors (transforming growth factor alpha) that would interact with overactive EGF receptors, producing a proliferative reaction." In this hypothesis, "A few immune cells came along for the ride," Dr. Krueger explained. He is D. Martin Carter Professor in Clinical Investigation at Rockefeller University.
Based on biopsies, "It's clear that psoriasis represents a big change in biology from background skin. There's a tremendous epidermal thickening reaction, on a bed of mononuclear inflammatory cells in the infiltrate." Immunohistochemical (Ki67) staining of hyperkeratotic skin invariably shows that virtually every basal cell is in cycle, versus very few basal cells in background skin. This growth activation is also associated with incomplete differentiation — this is a wound-healing program called regenerative maturation."
The second invariable feature in psoriasis is a large infiltrate of T cells — mostly CD4+ in the dermis, and CD8+ in the epidermis, Dr. Krueger says. Consistent overexpression of T cells led immunologists to theorize that psoriasis must involve an inductive reaction provoked by T cells with abundant high-affinity IL-2 receptors, he says.