Figure 2.

Role of γδT cells in the immune pathogenesis of psoriasis. Keratinocytes in the epidermis undergo apoptosis, necrosis, or death when exposed to certain external stimulation. With the release of cell contents, such as DNA and RNA, keratinocytes release antimicrobial peptides, such as LL-37. LL-37 binds with DNA and RNA to form a complex, promote immature DC activation, and secrete IFN-γ/IL-23 through the TLR7/8/9 pathway. IL-23 activates RORγt+γδT cells to secrete IL-17. γδT cell-derived IL-17 directly inhibits IGF-1 production in DETCs by increasing epidermal IL-23/IL-1β expression. During excessive keratinocyte proliferation, the secretion of TNF-α and chemokine ligand 20 (CCL20) increases, which consequently recruits CCR6+γδT cells to the inflammatory site of the epidermis. IL-17 cytokines produced by γδT cells potently upregulate the chemokine, CCL20, in keratinocytes, which chemoattracts IL-17A-producing CCR6+ immune cells to the inflamed site, thus forming a positive feedback loop. Il-23/IL-17 also promotes the recruitment of neutrophils to inflammatory sites, leading to excessive proliferation of the stratum corneum to form psoriatic inflammatory lesions. γδT cells have memory properties and can migrate rapidly to inflammatory sites through the blood and skin when subjected to a secondary stimulation. This consequently gives rise to severe inflammatory manifestations.