In mice, the CXCL10-binding chemokine receptor CXCR3 was shown to play a crucial role in the recruitment of autoaggressive T cells to pancreatic islets [24,25]. CXCL10 is produced by β cells  and increasingly detectable in serum of newly diagnosed or prediabetic subjects . Inhibition of CXCL10 homing to islets prevents autoimmune diabetes in experimental models [25,27]. CXCL10 production by islets of type 2 diabetes patients has been described and claimed to impair β cell function . Our observed CXCL10 and CXCR3 expression in pancreatic islets of a new-onset type 1 diabetes patient with enterovirus infection in β cells is strikingly similar to a very recent
report on fulminant diabetes and enterovirus infection . A role for CXCL10 and CXCR3 was proposed in which enterovirus infection of the pancreas initiated co-expression of CXCL10 in β cells, attracting autoreactive T cells and macrophages GW-572016 solubility dmso to the islets via CXCR3. We described the expression of this particular chemokine receptor on human autoreactive T cell clones obtained from peripheral blood samples of (pre)diabetic individuals and demonstrated their capacity to home to pancreatic tissue of NOD/SCID mice after adoptive transfer . In addition, recruited T cells
were found to express CXCR3 in situ, suggesting that peripheral blood T cells display the proper homing receptors, which is an important check-point for participation in the Stem Cell Compound Library process of insulitis and also perhaps in β cell destruction. Indeed, a type 1 diabetes patient-derived autoreactive CD8 T cell clone against preproinsulin, which was shown
to kill human pancreatic β cells, selectively expressed CXCR3 . The CXCL10–CXCR3 pathway facilitating leucocyte migration to pancreatic islets is active in all donors, but not in non-diabetic controls. This may provide the basis for the development of a novel therapeutic target in type 1 diabetes [24,25,27]. Our report underscores the value of extensive studies on human insulitis [31–34]. Indeed, the Juvenile Diabetes Research Foundation has launched IKBKE an initiative to collect pancreatic tissue from diabetic donors to facilitate and drive such studies that are likely to bridge the gap in knowledge on immune as well as environmental factors contributing to β cell destruction in human type 1 diabetes (http://www.jdrfnpod.org/). These studies were supported by the Juvenile Diabetes Research Foundation, the Dutch Diabetes Research Foundation, the Italian Ministries of Health, University and Research and the Italian Diabetes Society Research Foundation (FORISID). Printing of the colour graphs was supported by a donation from the Lugtenburg family. The authors declare no conflict of interest. “
“The identification of soluble factors involved in stem cell renewal is a major goal in the assessment of the BM niche.