期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms24098000
关键词
relapsing-remitting multiple sclerosis (RRMS); IL-27; myeloid dendritic cells (mDCs); lymphoproliferative assay; Programmed Death Ligand 2 (PD-L2); Programmed Death 1 receptor (PD1); innate immune response
The study examined whether myeloid dendritic cells (mDCs) from multiple sclerosis (MS) patients and healthy controls (HCs) become similarly tolerogenic when exposed to IL-27. The results showed that mDCs from HCs but not untreated MS patients became functionally tolerogenic after IL-27 treatment. Gene expression analysis identified different responses to IL-27 between HCs and MS patients, suggesting potential targets for regulating mDC tolerogenic responses.
The purpose of this study was to examine whether myeloid dendritic cells (mDCs) from patients with multiple sclerosis (MS) and healthy controls (HCs) become similarly tolerogenic when exposed to IL-27 as this may represent a potential mechanism of autoimmune dysregulation. Our study focused on natural mDCs that were isolated from HCs and MS patient peripheral blood mononuclear cells (PBMCs). After a 24-h treatment with IL-27 +/- lipopolysaccharide (LPS), the mDCs were either harvested to identify IL-27-regulated gene expression or co-cultured with naive T-cells to measure how the treated DC affected T-cell proliferation and cytokine secretion. mDCs isolated from HCs but not untreated MS patients became functionally tolerogenic after IL-27 treatment. Although IL-27 induced both HC and untreated MS mDCs to produce similar amounts of IL-10, the tolerogenic HC mDCs expressed PD-L2, IDO1, and SOCS1, while the non-tolerogenic untreated MS mDCs expressed IDO1 and IL-6R. Cytokine and RNA analyses identified two signature blocks: the first identified genes associated with mDC tolerizing responses to IL-27, while the second was associated with the presence of MS. In contrast to mDCs from untreated MS patients, mDCs from HCs and IFNb-treated MS patients became tolerogenic in response to IL-27. The genes differentially expressed in the different donor IL-27-treated mDCs may contain targets that regulate mDC tolerogenic responses.
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