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A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes.

Ferreira RC, Guo H, Coulson RM, Smyth DJ, Pekalski ML, Burren OS, Cutler AJ, Doecke JD, Flint S, McKinney EF, Lyons PA, Smith KG, Achenbach P, Beyerlein A, Dunger DB, Clayton DG, Wicker LS, Todd JA, Bonifacio E, Wallace C, Ziegler AG - Diabetes (2014)

Bottom Line: Previous epidemiological and genetic data have associated viral infections and antiviral type I interferon (IFN) immune response genes with T1D.Upregulation of IFN-inducible genes was transient, temporally associated with a recent history of upper respiratory tract infections (P = 0.0064), and marked by increased expression of SIGLEC-1 (CD169), a lectin-like receptor expressed on CD14(+) monocytes.DNA variation in IFN-inducible genes altered T1D risk (P = 0.007), as exemplified by IFIH1, one of the genes in our IFN signature for which increased expression is a known risk factor for disease.

View Article: PubMed Central - PubMed

Affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.

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Time-course of the expression of six IFN-inducible proteins on the surface of CD14+ monocytes. Surface expression of the IFN-inducible proteins SIGLEC-1, IL-15R, PD-L1, TRAIL, CD69, and CD38 was measured by flow cytometry on CD14+ monocytes. PBMCs isolated from a healthy donor were cultured with IFN-α (10 ng/mL; red line), IFN-β (10 ng/mL; blue line), or culture medium (unstimulated; black line). Protein expression was quantified on CD14+ monocytes at 3, 6, 24, 72, 120, and 168 h after stimulation. MFI, median fluorescence intensity.
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Figure 6: Time-course of the expression of six IFN-inducible proteins on the surface of CD14+ monocytes. Surface expression of the IFN-inducible proteins SIGLEC-1, IL-15R, PD-L1, TRAIL, CD69, and CD38 was measured by flow cytometry on CD14+ monocytes. PBMCs isolated from a healthy donor were cultured with IFN-α (10 ng/mL; red line), IFN-β (10 ng/mL; blue line), or culture medium (unstimulated; black line). Protein expression was quantified on CD14+ monocytes at 3, 6, 24, 72, 120, and 168 h after stimulation. MFI, median fluorescence intensity.

Mentions: We found no evidence for differential expression of the other five surface markers in any of the assessed immune subsets 24–72 h after stimulation. In contrast, SIGLEC-1 expression on monocytes increased linearly with IFN-α or IFN-β stimulation during up to 7 days of culture (Fig. 6), suggesting that expression of this protein is sustained for a long period of time following an IFN response.


A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes.

Ferreira RC, Guo H, Coulson RM, Smyth DJ, Pekalski ML, Burren OS, Cutler AJ, Doecke JD, Flint S, McKinney EF, Lyons PA, Smith KG, Achenbach P, Beyerlein A, Dunger DB, Clayton DG, Wicker LS, Todd JA, Bonifacio E, Wallace C, Ziegler AG - Diabetes (2014)

Time-course of the expression of six IFN-inducible proteins on the surface of CD14+ monocytes. Surface expression of the IFN-inducible proteins SIGLEC-1, IL-15R, PD-L1, TRAIL, CD69, and CD38 was measured by flow cytometry on CD14+ monocytes. PBMCs isolated from a healthy donor were cultured with IFN-α (10 ng/mL; red line), IFN-β (10 ng/mL; blue line), or culture medium (unstimulated; black line). Protein expression was quantified on CD14+ monocytes at 3, 6, 24, 72, 120, and 168 h after stimulation. MFI, median fluorescence intensity.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4066333&req=5

Figure 6: Time-course of the expression of six IFN-inducible proteins on the surface of CD14+ monocytes. Surface expression of the IFN-inducible proteins SIGLEC-1, IL-15R, PD-L1, TRAIL, CD69, and CD38 was measured by flow cytometry on CD14+ monocytes. PBMCs isolated from a healthy donor were cultured with IFN-α (10 ng/mL; red line), IFN-β (10 ng/mL; blue line), or culture medium (unstimulated; black line). Protein expression was quantified on CD14+ monocytes at 3, 6, 24, 72, 120, and 168 h after stimulation. MFI, median fluorescence intensity.
Mentions: We found no evidence for differential expression of the other five surface markers in any of the assessed immune subsets 24–72 h after stimulation. In contrast, SIGLEC-1 expression on monocytes increased linearly with IFN-α or IFN-β stimulation during up to 7 days of culture (Fig. 6), suggesting that expression of this protein is sustained for a long period of time following an IFN response.

Bottom Line: Previous epidemiological and genetic data have associated viral infections and antiviral type I interferon (IFN) immune response genes with T1D.Upregulation of IFN-inducible genes was transient, temporally associated with a recent history of upper respiratory tract infections (P = 0.0064), and marked by increased expression of SIGLEC-1 (CD169), a lectin-like receptor expressed on CD14(+) monocytes.DNA variation in IFN-inducible genes altered T1D risk (P = 0.007), as exemplified by IFIH1, one of the genes in our IFN signature for which increased expression is a known risk factor for disease.

View Article: PubMed Central - PubMed

Affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.

Show MeSH
Related in: MedlinePlus