2.3.1.2　Pathogenesis

Involvement of the immune system in psoriasis is now widely accepted.Genome-wide scans for psoriasis associated genes have identified predominantly immunerelated genes providing a mechanistic link between genetics and immunity.Psoriatic skin lesions originate as a result of dysregulated interactions of innate and adaptive components of the immune system with resident cutaneous cell types.Research about the immunopathogenesis of psoriasis has resulted in several highly specific therapies that target components of the immune system.Now there are several mechanisms of the disease：cross-talk between innate and adaptive immunities and the central role of TNF-a；the interleukin-23（IL-23）/T helper cell 17（Th17）axis（Figure 2-9）.

1.Cross-talk between innate and adaptive immunities

Psoriasis is mainly a dendritic cell-and T cell-mediated disease with complex feedback loops from antigen-presenting cells，neutrophilic granulocytes，keratinocytes，vascular endothelial cells，to the cutaneous nervous system.Cross-talk between the innate and the adaptive immune systems mediated by cytokines including TNF-α，interferon-y，and interleukin-1 is a major research focus.Complexes of host DNA and the epidermis-produced antimicrobial peptide LL-37（cathelicidin）are thought to stimulate dermal plasmacytoid dendritic cells to produce interferon-α.On exacerbation or onset of psoriasis，activated dendritic cells produce，among other mediators，TNF-α and interleukin-23.TNF-α is a proinflammatory cytokine that amplifies inflammation through several distinct pathways.TNF-α is produced by a broad range of cell types including macrophages，lymphocytes，keratinocytes，and endothelial cells，and exerts its activities on several different cell types.TNF-α induces secondary mediators and adhesion molecules，all of which have been implicated in psoriatic disease.The clinical success of TNF-blocking agents is therefore not surprising.(https://www.daowen.com)

2.IL-23/Th17 axis

Interest is rising in the IL-23/Th17 axis in psoriasis，which has resulted in several novel targeted therapies.Th17 are a subset of T cells expressing IL-17，distinct from the classical Th17 that play a predominant role in the pathogenesis of psoriasis and other inflammatory disorders.Expansion and survival of these T cells depends on myeloid cell-produced IL-23，which drives the differentiation of Th17.IL-23 acts mainly on memory T cells，because naive T cells do not express the IL-23 receptor.Once activated，Th17 produce several mediators such as IL-17A，IL-17F，and IL-22，which induce keratinocytes proliferation and other hallmark features of psoriasis.In psoriatic skin，IL-17 is produced by CD4+T cells，epidermal CD8+T cells，neutrophils，mast cells，and macrophages，which might explain the broad and rapid clinical efficacy of specifically targeting IL-17.