Gender-biased regulation of human IL-17-producing cells in vitro by peptides corresponding to distinct HLA-DRB1 allele-coded sequences.

Luz P Blanco, Melissa Plegue, Wai-Ping Fung-Leung, Joseph Holoshitz
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引用次数: 14

Abstract

Susceptibility to rheumatoid arthritis (RA) is associated with HLA-DRB1 alleles coding a 5-amino acid sequence motif called the shared epitope (SE). To explore the potential mechanisms that lead to RA susceptibility, we analyze the in vitro effect of peptides bearing different HLA-DR4 sequences on human peripheral blood-derived cells. Three 15-mer peptides were used: 65-79*0401 (an HLA-DRB1*04:01-coded sequence carrying the SE motif, QKRAA); 65-79*0402 (an HLA-DRB1*04:02-coded sequence carrying a SE-negative motif, DERAA); 65-79*0403 (an HLA-DRB1*04:03-coded sequence carrying a SE-negative motif, QRRAE). We found that CD4 TH17 cells are regulated by peptide treatment with gender bias. In male-derived T cells, all peptide treatments significantly reduced TH17 cell differentiation in vitro when compared to no peptide treatment, and to female samples. TH17 differentiation in samples not treated with peptides, either in the presence or absence of TH17-polarizing cytokines, was higher in males than in females; however, in unfractionated PBMC after treatment with TH17 polarizing cytokines, IL-17A positive cells were more abundant in females than in males. In addition, SE-positive females showed a significantly higher percentage of IL-17A-positive cells compared to SE-negative females. In conclusion, donor's SE status and gender may both influence TH17 immune polarization.

不同HLA-DRB1等位基因编码序列对应的多肽对人il -17产生细胞的体外性别偏见调控
类风湿关节炎(RA)的易感性与HLA-DRB1等位基因编码一个称为共享表位(SE)的5个氨基酸序列基序有关。为了探索导致RA易感性的潜在机制,我们分析了具有不同HLA-DR4序列的肽对人外周血源性细胞的体外作用。使用3种15-mer肽:65-79*0401 (HLA-DRB1*04:01编码序列,携带SE motif, QKRAA);65-79*0402 (HLA-DRB1*04:02编码序列,携带se阴性基序DERAA);65-79*0403 (HLA-DRB1*04:03编码序列,携带se阴性基序,QRRAE)。我们发现CD4 TH17细胞受多肽处理的性别偏倚调节。在男性来源的T细胞中,与无肽处理和女性样本相比,所有肽处理都显著降低了TH17细胞的体外分化。在未使用肽处理的样品中,无论是否存在TH17极化细胞因子,男性TH17分化高于女性;然而,在未分离的PBMC中,经TH17极化细胞因子处理后,IL-17A阳性细胞在女性中比在男性中更丰富。此外,与se阴性的雌性相比,se阳性的雌性显示出更高的il - 17a阳性细胞百分比。综上所述,供体SE状态和性别都可能影响TH17免疫极化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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