类风湿关节炎血液中 CD1c 树突状细胞耗竭并伴有新的 HLA-DRhi 表型

Christian Geier, Haani Qudsi, Jihad Ben Gabr, Robert J Winchester, Andras Perl
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摘要

类风湿性关节炎(RA)是一种导致滑膜关节和其他器官发炎的自身免疫性疾病。许多类风湿性关节炎患者在抗原递呈细胞(APC)上表达的 HLA-DR (DR) 分子中 "共享 "一个共同的肽序列,这表明 DRhi 细胞在类风湿性关节炎中很重要。在此,我们使用 DRhi 对 RA APC 进行了广泛定义和免疫分型,包括不符合标准定义的潜在 APC,如 RA 患者和健康对照组(HC)的淋巴细胞、单核细胞、树突状细胞(DC)。我们测量了与 DC(CD141、CD1c、CD11c、CD123、CD303)、单核细胞(CD14、CD16)、粒细胞标志物(CD15、CCR3)、共刺激分子和趋化因子受体相关的分子的平均荧光强度(MFI)。在 RA 中,DC2(CD1c+)显示较高的 CD56、CD86、CD275 和 CCR7。RA中的DC2频率要低得多:RA中DRhi的3.2%[IQR 2.41至4.46]与HC中的6.9%[IQR 3.96至9.08]相比;P=0.005。CD15 在所有 RA APC 亚群中都有所增加(p<0.01)。在 RA 中出现了一个独特的 CD15+CD16+ 群体,占白细胞的 1.5% [IQR 0.68 至 3.32](在 HC 中为 0.1% [IQR 0.08 至 0.46];p<0.001),平均占总 DRhi 的 2.34%。CD15+CD16+ 亚群为 CD303+、CD83+ 和 CD275+,而 CD123 相对于参考浆细胞 DC 要少得多(p<0.01)。总之,RA 中 APC 的改变包括 DC2 的耗竭和 CD15 的增加。此外,RA 中的 APC(DRhi)区系包含具有共同的树突状细胞和粒细胞特征的细胞;这种表型表明,这些明显的 APC 可能通过向 CD4+ T 淋巴细胞呈递自身抗原而参与类风湿性关节炎的病理生理学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CD1c Dendritic Cells are depleted and accompanied by new HLA-DRhi Phenotypes in Rheumatoid Arthritis Blood
Rheumatoid arthritis (RA) in an autoimmune disease that leads to inflammation of synovial joints and other organs. Many RA patients "share" a common peptide sequence within the HLA-DR (DR) molecule expressed on antigen-presenting cells (APC), suggesting that DRhi cells are important in RA. Here, we use DRhi to broadly define and immunophenotype RA APC, including potential APC not meeting standard definitions for lymphocytes, monocytes, dendritic cells (DC) from RA patients and healthy controls (HC). We measured mean fluorescence intensities (MFI) of molecules associated with DC (CD141, CD1c, CD11c, CD123, CD303), monocytes (CD14, CD16); granulocytic markers (CD15, CCR3), co-stimulatory molecules and chemokine receptors. DC2 (CD1c+) showed higher CD56, CD86, CD275, and CCR7 in RA. DC2 frequencies were much lower in RA: 3.2% of DRhi [IQR 2.41 to 4.46] in RA vs. 6.9% [IQR 3.96 to 9.08] in HC; p=0.005. CD15 was increased in all RA APC subsets (p<0.01). A distinct CD15+CD16+ population appeared in RA, representing 1.5% of leukocytes [IQR 0.68 to 3.32] (vs 0.1% in HC [IQR 0.08 to 0.46]; p<0.001) and contributed a mean of 2.34% to overall DRhi. The CD15+CD16+ subset was CD303+, CD83+ and CD275+ with much less CD123 relative to reference plasmacytoid DC (p<0.01). In conclusion, APC alterations in RA include depletion of DC2 and increased CD15. Moreover, the APC (DRhi) compartment in RA contains cells with shared dendritic cell and granulocytic features; this phenotype suggests these apparent APC may participate in the pathophysiology of rheumatoid arthritis via the presentation of self-antigen(s) to CD4+ T lymphocytes.
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