期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.750162
关键词
DC-10; type 1 diabetes (T1D); HLA-G; tolerogenic dendritic cells; pro-inflammatory myeloid cells; first-degree relatives (FDRs)
类别
资金
- Italian Telethon Foundation [TGT16-17G01]
- JDRF Innovation [1-PNF-2015-110-S-B]
- JDRF Strategic Research Agreement (SRA)-JDRF International TrialNet Clinical Center in Italy [3-SRA 2015-29-Q-R]
DC-10, a subset of human dendritic cells involved in IL-10-mediated tolerance and naturally expressing HLA-G, may serve as a potential marker for stratifying individuals at risk of developing Type 1 diabetes (T1D). The alteration in DC-10 number and phenotype during T1D development is associated with an increased risk of the disease, suggesting a possible use of CD83(+) DC-10 as a prognostic factor.
Type 1 diabetes (T1D) is a chronic autoimmune disease resulting in progressive destruction of beta-cells. Several factors affecting lymphocyte and antigen-presenting cells, including dendritic cells (DCs), contribute to defective maintenance of tolerance in T1D. DC-10 are a subset of human DCs involved in IL-10-mediated tolerance. A precise monitoring of DC-10 in the peripheral blood is possible thanks to the discovery of specific biomarkers. DC-10, being cells that naturally express HLA-G, may be used for the appropriate staging of the disease. By enumerating and phenotypically characterizing DC-10 in the peripheral blood of subjects at different stages of T1D development-first-degree relatives (FDRs) of T1D patients, without (Ab(neg)) or with (Ab(pos)) autoantibodies, T1D patients at onset, and age-matched healthy controls (HCs)-we showed that DC-10 contain a high proportion of HLA-G-expressing cells as compared with monocytes. We reported that a low frequency of DC-10 during disease development is paralleled with the increased proportion of pro-inflammatory cDC2 cells. Moreover, DC-10 number and phenotype differ from Ab(neg) FDRs, Ab(pos) FDRs, and T1D patients compared with HCs, and DC-10 from T1D patients express low levels of CD83. Finally, multiple regression analysis, considering DC-10 and HLA-G-related parameters, showed that Ab(neg) FDRs are more similar to subjects with autoimmunity than to HCs. This is the first demonstration that impairment in DC-10 number and phenotype, specifically CD83 expression, is associated with risk of developing T1D, suggesting a possible use of CD83(+) DC-10 to stratify individuals at risk of T1D in conjunction with classical prognostic factors.
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