Fig. 6: The immunology of psoriasis. Immune activation occurs as APC process antigen, become activated, migrate to the local skin-draining lymph node and stimulate naïve T-cells to become activated memory T-cells expressing a TC1 or TH1 phenotype, which can then return to the skin via expression of CLA and LFA-1 (Figs. 4 and 5). (1) These activated T-cells express inflammatory cytokines TNF- and IFN- which can (2) induce keratinocytes to produce adhesion molecules such as ICAM-1, costimulatory molecules such as CD40 and MHC II molecules for antigen presentation, facilitating further T-cell/keratinocyte interactions. (3) TNF- also induces keratinocytes to produce vascular endothelial cell growth factor (VEGF) which causes endothelial cell proliferation, increased ICAM/VCAM expression and subsequent increased recruitment of activated T-cells. Keratinocytes also produce other proinflammatory cytokines such as IL-1 and IL-6 that are involved in regenerative responses. (4) Ongoing antigen stimulation between activated APC and T-cells can occur in the epidermis without the need for further APC migration to the lymph node. This is skewed to the TC1/TH1 phenotype by IL-12 produced by the APC. IFN- and TNF- that are continually produced result in a regenerative phenotype of the keratinocytes, manifested as (5) epidermal hyperproliferation with elongation of the rete ridges, loss of the granular layer and retained nuclei in the stratum corneum (parakeratosis). (6) TNF- also induces keratinocytes to produce IL-8 that is chemotactic for neutrophils. Photo: Chesley Sheppard