Abstract
It is broadly accepted that psoriasis is an immune-mediated disease with a heritable component, but it is not clear what causes inflammation in the skin. Previous research suggests that fragments of the keratin 17 (K17) protein, which are constitutively expressed in hair follicles, could act as autoantigens. In this study, we synthesized the K17 protein from mRNA derived from hair follicles and tested whether it elicited T cell responses depending on the patient genotype at the major susceptibility locus HLA-Cw*06:02. We treated peripheral blood-derived cells with the K17 protein and its short fragments to assess the T cell proliferation response using flow cytometry. Our analyses show a significantly stronger increase in cell proliferation among patients but not in healthy controls. We then examined whether the variation in T cell proliferation correlated with the patient HLA-Cw*06:02 risk genotype. Considering the affected status and patient genotype as two independent predictors, we fitted a linear model and showed that the HLA-Cw*06:02 allele dosage strongly predicted the T cell response. Our study findings suggest that the K17 protein likely acts as an autoantigen in psoriasis and that patients’ risk genotype is strongly correlated with the magnitude of the response to this putative autoantigen.
Highlights
Psoriasis is an immune-mediated chronic skin disease with a complex aetiology involving both genetic risk factors and environmental triggers
We evaluated whether hair follicle-derived keratin 17 can elicit an immune response in psoriasis patients and whether their genotype at the HLA-Cw*06:02 locus can predict the strength of the response to this putative autoantigen
Verified pGEX4T1-keratin 17 (K17), pGEX4T1-S1 or pGEX4T1-S4 plasmids were successfully transformed into E. coli BL21 cells, and bacterial cells were induced to express recombinant proteins using IPTG
Summary
Psoriasis is an immune-mediated chronic skin disease with a complex aetiology involving both genetic risk factors and environmental triggers. The putative mechanism of inflammation could be similar to those observed in acute rheumatic fever and rheumatic heart disease In this disease, streptococcal superantigen (GAS) circulating in the infected organism disrupts host immune tolerance and increases infiltration of GAS activated immune cells into the target tissue[9]. The expression level of K17 protein is normally low but increases in response to injury during tissue repair and cell division[16,17] In this regard, the protein is constitutively expressed in hair follicles and nail beds - two sites that often first develop psoriasis lesions[14]. We genotyped the major genetic susceptibility HLA-Cw*06:02 locus[18] in psoriasis patients and healthy controls and studied their cell-based immune response against the putative autoantigen K17. We evaluated whether hair follicle-derived keratin 17 can elicit an immune response in psoriasis patients and whether their genotype at the HLA-Cw*06:02 locus can predict the strength of the response to this putative autoantigen
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