Polymorphisms in the FOXP3 gene in Han Chinese psoriasis patients.
ABSTRACT Psoriasis is a common dermatological disorder, in which autoimmunity plays an important role. CD4(+)CD25(+) regulatory T cells (T-regs) have been suggested to be involved in the pathogenesis of some autoimmune diseases. T-regs express the fork head/winged helix transcription factor, FOXP3, which appears to be of key importance in the development and function of T-regs. Studies have found that single-nucleotide polymorphisms (SNPs) in the FOXP3 gene contribute to susceptibility to some autoimmune disorders. However, information about FOXP3 gene in psoriasis is limited.
This study evaluated the association between FOXP3 gene SNPs and susceptibility to psoriasis in a Han Chinese population.
In a hospital-based case-control study, 524 patients with psoriasis and 549 psoriasis-free controls were recruited according to age and gender. We investigated four SNPs in the FOXP3 gene (-6054, deletion/ATT; -3279, A/C; -924, A/G; IVS9+459, A/G) in psoriatic patients, and assessed allele and genotype frequencies in psoriatic patients (237 females, 287 males) and normal controls (272 females, 277 males). The polymorphisms were genotyped using the PCR sequence-specific primer (PCR-SSP) technique and PCR-restriction fragment length polymorphism (RFLP) analysis.
We found that increased risk of psoriasis was associated with the FOXP3 -3279 AC genotype (adjusted OR, 1.32; 95% CI, 1.01-1.74) and the combined AC+AA genotype (adjusted OR, 1.38; 95% CI, 1.07-1.78), compared with the -3279 CC genotype. We also found that an increased risk of psoriasis was associated with the FOXP3 IVS9+459 GG genotype (adjusted OR, 2.24; 95% CI, 1.41-3.58). However, the combined GA+GG genotype showed no such tendency (adjusted OR=1.28; 95% CI, 1.00-1.64), compared with the IVS9+459 AA genotype. There was no evidence of an increased risk associated with the FOXP3-6054 deletion/ATT or FOXP3-924 A/G genotype. In combined genotype analyses, the FOXP3-3279 AC+AA genotype was more obviously associated in males (adjusted OR=1.60, 95% CI=1.11-2.31) and severe psoriasis patients (PASI score >20; adjusted OR=1.97, 95% CI=1.41-2.75). Meanwhile, the FOXP3 IVS9+459 GA+GG genotype was also associated with severe psoriasis patients (adjusted OR=1.69, 95% CI=1.21-2.36).
FOXP3 polymorphisms appear to contribute to the risk of psoriasis in a Han Chinese population. Larger studies are needed to confirm these findings.
Article: MHC-independent genetic factors control the magnitude of CD4+ T cell responses to amyloid-β peptide in mice through regulatory T cell-mediated inhibition.[show abstract] [hide abstract]
ABSTRACT: Accumulation of amyloid-β peptide (Aβ) is considered the triggering factor of pathogenic lesions in Alzheimer's disease (AD), and vaccines targeting Aβ are promising therapeutic options. However, the occurrence of meningoencephalitides attributed to T cell responses in 6% of Aβ-immunized patients underscores the need for a better understanding of T cell responses to Aβ. We characterized the parameters controlling the magnitude of Aβ-specific CD4(+) T cell responses in mice. T cell responsiveness to Aβ1-42 was highly heterogeneous between mouse strains of different H-2 haplotypes, with SJL/J (H-2(s)) mice displaying a strong response, mainly specific for Aβ10-24, and C57BL/6 (H-2(b)) mice displaying a weak response to Aβ16-30. Surprisingly, C57BL/6 mice congenic for the H-2(s) haplotype (B6.H-2(S)), which display a "permissive" MHC class II allele for presentation of the immunodominant Aβ10-24 epitope, showed a very weak CD4(+) T cell response to Aβ, suggesting that MHC-independent genes downmodulate Aβ-specific CD4(+) T cell responses in C57BL/6 background. Vaccine-induced CD4(+) T cell responses to Aβ were significantly enhanced in both C57BL/6 and B6.H-2(S) mice upon depletion of regulatory T cells (Tregs), whereas Treg-depleted SJL/J mice displayed unaltered Aβ-specific T cell responses. Finally, Treg depletion in C57BL/6 transgenic APPPS1 mice, a mouse model of AD, results in enhanced vaccine-induced CD4(+) T cell responses in AD compared with wild-type animals. We concluded that the magnitude of Aβ-specific CD4(+) T cell responses is critically controlled in both physiological and pathological settings by MHC-independent genetic factors that determine the overall potency of Aβ-specific Treg responses.The Journal of Immunology 09/2011; 187(9):4492-500. · 5.79 Impact Factor