The proliferation rate decreased towards values nearer to those observed in H-MSCs and the secretion of the cytokines that mostly identified the inflammatory microenvironment that characterized psoriasis, such as interleukin (IL)-6, IL-12, IL-13, IL-17A, tumour necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (G-CSF), is significantly lower in co-cultured PsO-MSCs than in individually cultured PSO-MSCs (P at least < 0·05).
Our comparison of a stratified population with type I psoriasis (n = 155) and healthy controls (N = 197) is the first to reveal a relationship between the CLMN, FBXL19, CCL4L, C17orf51, TYK2, IL13, SLC22A4, CDKAL1, and HLA-B/MICA genes.
The use of genome-wide association studies has highlighted novel genes associated with the development of psoriasis as IL12B, IL23R, TNFAIP3 and IL13 for instance.
ZNF313 and IL-13 are associated with risk for psoriasis in a Chinese Uygur population, and there is an effect of interaction between the two genes on this risk.
Evidence for an association between EBV-negative cHL and rs20541 (5q31, IL13: OR = 1.53, 95% CI = 1.32 to 1.76, P = 5.4 x 10(-9)), a variant previously linked to psoriasis and asthma, was observed; however, the evidence for replication was less clear.
The authors genotyped three groups of Caucasians: those with PsA, those with psoriasis without arthritis (PsC) and healthy controls for the rs20541 and rs848IL13 single nucleotide polymorphisms (SNPs).
Psoriasis and psoriatic arthritis fall into this disease spectrum, with the largest region of susceptibility coming from the MHC (most likely HLA-C, ie, C*06:02 although additional influences are also being implicated), and most of the other genetic susceptibility coming from genes involved in cytokine production, specifically genes in the Th17 pathway (IL-12B, IL-23A and IL-23R, the latter, like in AS, not seen in Asians), genes in the nuclear factor κB pathway (TNFAIP3 and TNIP1) and genes in the Th2 pathway (IL-4 and IL-13).
Recently, the results of multiple well-powered genome-wide association studies have identified several additional loci outside the major histocompatibility complex region associated with psoriasis risk, including three genes involved in interleukin (IL)-23 signaling (IL-23R, IL-23A, IL-12B), two genes that regulate nuclear factor-kappaB signaling (TNIP1, TNFAIP3), and two genes involved in the modulation of T-helper type 2 immune responses (IL-4, IL-13).
Association with psoriasis and psoriatic arthritis has been found in TNFAIP3 and TNFIP1, ubiquitin ligases in the NF-kappaB pathway, and IL13, a Th2 cytokine.
Similarly, association of the 5q31 gene region encompassing the IL13 gene has been reported with PsA but not psoriasis by one group, but this awaits confirmation in other series.
Although functional variants remain to be identified, we speculate that genetic variants at the IL4/IL13 locus contribute to the Th1 bias that is characteristic of psoriasis, that Th1-derived IFN-gamma supports expansion of IL-17+ T cells through APC-derived IL-23 and that negative regulation of inflammatory signaling through the NF-kappaB axis is impaired because of genetic variants of TNFAIP3 and TNIP1.