Differential transcriptome of tolerogenic versus inflammatory dendritic cells points to modulated T1D genetic risk and enriched immune regulation
Differential transcriptome of tolerogenic versus inflammatory dendritic cells points to modulated T1D genetic risk and enriched immune regulation
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DOI：
10.1038/gene.2017.18
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发表时间：
2017-09-01
影响因子：
5
通讯作者：
Roep, B. O.
中科院分区：
文献类型：
--
作者：
Nikolic, T.;Woittiez, N. J. C.;Roep, B. O.
耐受性树突状细胞(TolDC)被认为是调节自身免疫的免疫佐剂。支持其调控功能的潜在基因表达仍然不明确。采用基因测序的方法，比较了非调控成熟炎性树突状细胞(1，25-dihydroxyvitaminD(3)/dexametasone-modulated-TolDC，MDCs)的转录水平。差异表达的基因控制细胞间的相互作用、代谢途径，并支持tolDCs通过营养和信号剥夺调节细胞激活的能力，共同将tolDCs连接成耐受性免疫调节器。基因表达差异与蛋白表达相关，表明细胞表面低CD86和高CD52是tolDC和mdcs的更好的鉴别指标。在发生1型糖尿病(T1D)的37个候选基因中，有11个基因在TolDC和MDCS中差异表达，调节免疫反应和抗原提呈活性。T1D候选风险基因的差异表达转录本表明，这些风险基因在免疫调节中发挥作用，靶向可能调节自身免疫的遗传贡献。
Tolerogenic dendritic cells (tolDCs) are assessed as immunomodulatory adjuvants to regulate autoimmunity. The underlying gene expression endorsing their regulatory features remains ill-defined. Using deep mRNA sequencing, we compared transcriptomes of 1,25-dihydroxyvitaminD(3)/dexametasone-modulated tolDCs with that of non-modulated mature inflammatory DCs (mDCs). Differentially expressed genes controlled cellular interactions, metabolic pathways and endorse tolDCs with the capacity to regulate cell activation through nutrient and signal deprivation, collectively gearing tolDCs into tolerogenic immune regulators. Gene expression differences correlated with protein expression, designating low CD86 and high CD52 on the cell surface as superior discriminators between tolDCs and mDCs. Of 37 candidate genes conferring risk to developing type 1 diabetes (T1D), 11 genes differentially expressed in tolDCs and mDCs regulated immune response and antigen-presenting activity. Differential-expressed transcripts of candidate risk loci for T1D suggest a role of these 'risk genes' in immune regulation, which targeting may modulate the genetic contribution to autoimmunity.