Aims/hypothesisType 1 diabetes is an autoimmune disorder characterised by loss of insulin-producing beta cells of the pancreas. Progress in understanding the cellular and molecular mechanisms underlying the human disease has been hampered by a dearth of appropriate human experimental models. We previously reported the characterisation of islet-infiltrating CD4+ T cells from a deceased organ donor who had type 1 diabetes.MethodsInduced pluripotent stem cell (iPSC) lines derived from the above donor were differentiated into CD14+ macrophages and tested for their capacity to present antigen to T cell receptors (TCRs) derived from islet-infiltrating CD4+ T cells from the same donor.ResultsThe iPSC macrophages displayed typical macrophage morphology, surface markers (CD14, CD86, CD16 and CD11b) and were phagocytic. In response to IFNγ treatment, iPSC macrophages upregulated expression of HLA class II, a characteristic that correlated with their capacity to present epitopes derived from proinsulin C-peptide to a T cell line expressing TCRs derived from islet-infiltrating CD4+ T cells of the original donor. T cell activation was specifically blocked by anti-HLA-DQ antibodies but not by antibodies directed against HLA-DR.Conclusions/interpretationThis study provides a proof of principle for the use of iPSC-derived immune cells for modelling key cellular interactions in human type 1 diabetes.Electronic supplementary materialThe online version of this article (10.1007/s00125-019-04988-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Vitamin D has an important role to play in skeletal and extraskeletal health. Inspite of being a sun rich country, India has widespread vitamin D deficiency. Vitamin D deficiency can lead to serious consequences like hypocalcemic seizures and increased risk of respiratory tract infections in neonates and infants. International expert groups advocate universal supplementation for non-formula fed infants, pregnant and lactating women and those at risk of deficiency. A body of literature on vitamin D status in India is being generated, which may guide clinical practice in our country. Treatment of deficiency must be undertaken with minimally effective doses to avoid the risk of toxicity. Sensible sunshine exposure should be encouraged to facilitate vitamin D production from natural sources.
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