Current concepts in the pathogenesis of psoriasis

Area of Science:

• Immunodermatology
• Molecular Biology

Background:

• Psoriasis is a complex, multi-factorial skin disease.
• Its pathogenesis involves immune cells like T cells, antigen-presenting cells (APCs), and keratinocytes.
• Key cytokines and growth factors, including vascular endothelial growth factor (VEGF) and keratinocyte growth factor (KGF), are implicated.

Purpose of the Study:

• To elucidate the complex pathogenesis of psoriasis.
• To identify key cellular and molecular players in psoriatic lesion development.
• To explore the role of genetic predisposition and molecular mimicry.

Main Methods:

• Review of existing literature on psoriasis pathogenesis.
• Analysis of cellular interactions (T cells, APCs, keratinocytes, Langerhans' cells, macrophages, NK cells).
• Examination of cytokine profiles (Th1 type) and growth factors (VEGF, KGF).

Main Results:

• Psoriasis pathogenesis is hypothesized to initiate with T cell activation by an unknown antigen.
• Activated T cells, inflammatory cells, and keratinocytes secrete cytokines, driving keratinocyte hyper-proliferation.
• Langerhans' cells migrate to lymph nodes, activating naive T cells, potentially leading to memory cells reacting via molecular mimicry (e.g., with keratin).
• High concordance rates in monozygotic twins (63-73%) suggest a strong genetic component, with susceptibility loci (PSORS1-PSORS9) identified.

Conclusions:

• Psoriasis pathogenesis is a multifactorial process involving intricate immune cell crosstalk and keratinocyte hyper-proliferation.
• Genetic background and potential molecular mimicry are significant contributing factors.
• Understanding these mechanisms is crucial for developing targeted therapies for psoriasis.