Table 1.
The role of cytokines and chemokines in psoriasis
| Cytokine | Cellular source | Level in psoriasis | Biological effects in psoriasis | Ref. |
|---|---|---|---|---|
| IL-1β | Activated macrophages, DCs, KCs, and T cells | ↑ lesional skin | - Activates the pro-inflammatory response of KCs | [29–33] |
| - Promotes the formation of perivascular DCs clusters | ||||
| - Triggers TH17 cells differentiation | ||||
| - Induces proliferation of dermal γδ T cells | ||||
| IL-2 | DCs, activated T cells, macrophages | ↑ lesional skin | - T cells survival factor | [34] |
| - Promotes T cells differentiation into effector T cells or memory T cells | ||||
| IL-4 | Activated TH2 cells, basophils, mast cells, ILC2 | ↓ in psoriatic epidermal T cells | - Promotes TH2 immune response | [35–37] |
| - Suppresses TH1 and TH17 responses | ||||
| - Suppresses IL-1β and IL-6 production by KCs | ||||
| - Suppresses IL-23 production by DCs and promotes p35 production | ||||
| IL-6 | DCs, endothelial cells, KCs, T cells | ↑ lesional skin | - Promotes TH17 cells differentiation | [38–41] |
| ↑ serum of psoriasis patients | - Inhibits suppressive functions of Tregs | |||
| - Induces angiogenesis by upregulating VEGF production | ||||
| IL-7 | Hair follicle KCs | ↑ lesional skin | - Maintains CD4+ and CD8+ skin-resident memory T cells in the epidermis | [42–44] |
| ↑ serum of psoriasis patients | ||||
| IL-8 (CXCL8) | Neutrophils, KCs | ↑ lesional skin | - Stimulates neutrophil infiltration | [41, 45–47] |
| ↑ serum of psoriasis patients | - Induces KCs hyperproliferation | |||
| - Stimulates angiogenesis | ||||
| IL-9 | TH9 cells and TH22 cells | ↑ lesional skin | - Induces IL-17A production by CD4+ T cells | [48, 49] |
| ↑ plasma of psoriasis patients | - Stimulates angiogenesis | |||
| IL-10 | TH cells, monocytes, macrophages, and DCs | ↓ lesional skin | - Suppresses type 1 inflammation | [50] |
| ↑ serum of psoriasis patients | - Downregulates IL-8/CXCR2 pathway in epidermal cells | |||
| - Reduces KCs proliferation | ||||
| IL-11 | Fibroblasts, epithelial cells | ↑ lesional skin | - Reduces T cells infiltration | [51] |
| - Polarizes immune response towards type 2 response | ||||
| - Reduces KCs proliferation | ||||
| IL-12 | Activated DCs, macrophages, monocytes, and B cells | ↑ IL-12p40 and IL-12p70 in lesional skin | - Inhibits the invasion of γδT17 cells | [27, 33, 41, 52, 53] |
| ↑ serum of psoriasis patients | - Induces protective transcriptional program in KCs limiting skin inflammation | |||
| - No changes or decreased level of IL-12p35 | - Induces IFN-γ production by NK cells and T cells | |||
| - Promotes differentiation of TH1 cells | ||||
| IL-13 | Activated TH2 cells, mast cells, and basophils | ↑ lesional skin | - Functional role in psoriasis is unclear | [50, 54] |
| ↑ serum of psoriasis patients | ||||
| IL-15 | Hair follicle KCs | ⟷ serum of psoriasis patients | - Synergizes with IL-23 to induce IL-17F, IL-17A, and IFN-γ production by T cells | [44, 50, 55] |
| - Induces T cells infiltration | ||||
| - Stimulates angiogenesis | ||||
| IL-16 | KCs | ↑ serum of psoriasis patients | - Promotes recruitment of CD4+ T cells to psoriatic lesions | [56] |
| IL-17 | TH17 cells, Tc17 cells, NK cells, γδ T cells, mast cells, neutrophils | ↑ IL-17A, IL-17C, and IL-17F in lesional skin | - Increases the level of LL37 | [25, 27, 40, 49, 57–61] |
| - Promotes secretion of multiple proinflammatory cytokines, including IL-1β, IL-6, GM-CSF, and TNF | ||||
| - Upregulates production of chemokines | ||||
| - Impairs Tregs suppressive functions | ||||
| IL-18 | KCs | ↑ lesional skin | - Promotes infiltration of immune cells in psoriasiform inflammation | [27, 41, 62, 63] |
| ↑ serum of psoriasis patients | - Upregulates the expression of IL-17 and suppresses the expression of IL-4 in psoriatic skin | |||
| IL-19 | KCs | ↑ lesional skin | - Upregulates the expression of inflammatory mediators in KCs | [33, 60, 64] |
| ↑ serum of psoriasis patients | - Synergizes with IL-17A to induce production of β-defensin, IL-23p19, and TH17- and neutrophil-attracting chemokines | |||
| IL-20 | KCs, leukocytes | ↑ lesional skin | - Promotes angiogenesis and chemotaxis | [33, 60] |
| ↑ serum of psoriasis patients | - Promotes keratinocyte differentiation and activation | |||
| - Stimulates production of pro-inflammatory cytokines | ||||
| IL-21 | CD4+ T cells, especially TH17 cells | ↑ lesional skin | - Promotes KCs hyperproliferation | [33, 65–68] |
| ↑ serum of psoriasis patients | - Promotes and sustains TH17 cells differentiation | |||
| - Inhibits Tregs differentiation | ||||
| IL-22 | Mast cells, TH22 cells, TH17 cells, Tc cells, NK-T cells, γδ T cells, DCs, macrophages | ↑ lesional skin | - Stimulates KCs hyperproliferation, differentiation, and migration | [33, 58, 60, 69–73] |
| ↑ serum of psoriasis patients | - Induces the secretion of pro-inflammatory cytokines | |||
| IL-23 | Inflammatory monocytes, mature DCs, KCs | ↑ lesional skin | - Promotes TH17 activation, survival, and pathogenic potential | [53, 74–77] |
| - Activates dermal γδ T cells and promotes their expansion | ||||
| - Stimulates antigen presentation by DCs | ||||
| - Triggers IFN-γ production | ||||
| - Promotes immune cells infiltration to the skin | ||||
| - Triggers hyperplasia of KCs | ||||
| IL-24 | KCs, monocytes | ↑ lesional skin | - Induces psoriasis-like inflammation | [60, 78, 79] |
| IL-25 (IL-17E) | KCs | ↑ lesional skin | - Stimulates pro-inflammatory phenotype and proliferation of KCs | [33, 80] |
| - Stimulates infiltration of DCs, macrophages, and γδ T cells to the skin | ||||
| IL-26 | TH1 cells, TH17 cells, NK cells | ↑ lesional skin | - Promotes infiltration of neutrophils and CD4+ T cells into the skin | [58, 81, 82] |
| - Stimulates angiogenesis | ||||
| IL-33 | Epithelial cells, KCs, DCs | ↑ lesional skin | - Promotes pro-inflammatory phenotype of KCs | [83] |
| IL-36γ (IL-1FG) | KCs, monocytes, DCs | ↑ lesional skin | - Induces the expression of AMPs and matrix metalloproteinases (MMPs) by KCs | [60, 84–86] |
| - Regulates the recruitment of inflammatory cells and the expansion IL-17–producing γδ T cells in the skin | ||||
| IL-37 | Macrophages, effector memory T cells | ↓ lesional skin | - Inhibits the production of inflammatory mediators by KCs | [28, 87, 88] |
| IL-38 | KCs | ↓ lesional skin | - Suppresses psoriatic inflammation | [89, 90] |
| ↓ serum of psoriasis patients | - Suppresses pro-inflammatory phenotype of KCs | |||
| - Suppresses IL-17A production by dermal γδ T cells | ||||
| IFN-α | pDCs | ↑ lesional skin | - Induces TH1 and TH17cells and their activation and proliferation | [50, 91–93] |
| ↑ serum of psoriasis patients | - Activates DCs and KCs | |||
| IFN-β | KCs, pDCs | ↑ lesional skin | - Regulates KCs differentiation | [18, 91, 94] |
| - Promotes DCs activation and differentiation | ||||
| IFN-γ | T cells, NK cells | ↑ lesional skin | - Activates KCs | [27, 33, 41, 58, 95] |
| ↑ serum of psoriasis patients | - Promotes T cells infiltration | |||
| - Promotes DCs maturation | ||||
| TGF-β | Tregs | ↑ lesional skin | - Inhibits KCs proliferation | [96–99] |
| ↑ serum of psoriasis patients | - Promotes T cell infiltration | |||
| TNF-α | Activated T cells, DCs, macrophages, KCs, fibroblasts |
↑ lesional skin ↑ serum of psoriasis patients |
- Activates T cells, macrophages and DCs | [33, 41, 70, 95, 100–104] |
| - Activates KCs triggering hyperproliferation | ||||
| - Synergizes with IL-17A | ||||
| - Promotes secretion of pro-inflammatory cytokines | ||||
| - Induces infiltration of immune cells to the lesional skin | ||||
| - Promotes angiogenesis by inducing VEGF secretion |