Table 1.
Link between triggers incriminated in psoriasis occurrence and pathophysiological mechanisms.
| Trigger | Pathophysiological Mechanism | References |
|---|---|---|
| Mechanical stress | Nerve growth factor (NGF) associated with the Koebner phenomenon; upregulation of NGF in keratinocytes stimulates their proliferation | [33] |
| Tissue resident memory T cells (T RM), site-specific memory T cells in the skin | [34] | |
| Skin injury induces IFN-β secretion from keratinocytes, promoting Dendritic Cell (DC) maturation and T cell proliferation | [35] | |
| Psychological stress | Corticotropin-releasing hormone (CRH) that causes the degranulation of mastocytes and the release of TNF-α and IL-6 | [36] |
| High levels of corticosteroids (CS) stimulate 5-HT synthesis, increase 5-HT2AR (proinflammatory role, 5-HT-mediated recruitment of CD4+ lymphocytes), decrease 5-HT1AR (inhibitor of inflammation) | [37] | |
| Infection | Streptococcal superantigens-pyrogenic exotoxin and M protein stimulate T cells to produce IFN-γ | [38] |
| Molecular mimetism between M6 streptococcal protein and type I keratin | ||
| Staphylococcus aureus Enterotoxin-A (SEA) induces the production of IFN-γ in MHC class II positive T cell lines | [39] | |
| TAT gene promotes HIV replication and activates genes responsible for keratinocyte proliferation (IL-6, IL-2, TNF, TGFβ1, and Superoxide Dismutase (SOD)) | [38] | |
| HIV causes an imbalance in the CD4+/CD8+ ratio, leading to a proinflammatory cascade characteristic of psoriasis. CD8+ T cells and memory CD8+ move up in the dermis of lesioned skin, resulting in exacerbation of psoriasis | [40,41] | |
| Gp120 and nef HIV proteins act as superantigens | [42] | |
| HPV infection triggers an inflammatory state that causes upregulation of NGF | [43] | |
| Antibiotics | Tetracyclines photosensitize the skin, resulting in Koebnerization | [44] |
| Amoxicillin: Streptococcus pneumoniae exposed to β-lactam antibiotics stimulates macrophage release of TNF-α and IL-1β | ||
| Gut microbiome | Depletion of Short-Chain Fatty Acids (SCFA) antagonizes Treg differentiation and their suppressive activity and causes increased production of IL-23 via DCs | [45] |
| “Leaky gut syndrome”: higher levels of E. coli DNA in psoriasis patients suffering from exacerbation causes activation of Th17 lymphocytes | [46] |