Podoplanin is an inflammatory protein upregulated in Th17 cells in SKG arthritic joints.

Interleukin 17-producing helper T (Th17) cells play pathogenic roles in chronic inflammatory and autoimmune diseases, including arthritis, colitis and multiple sclerosis. Th17 cells selectively express the transcription factor RORγt, as well as the cytokine receptors IL-23R and CCR6. Identification of novel Th17 cell-specific molecules may have potential value as diagnostic markers in the above-mentioned inflammatory diseases. To that aim, we carried out a comparative microarray analysis on in vitro differentiated Th1, Th2, Treg and Th17 cells from naïve CD4(+) cells of BALB/c mice. Among a total of one hundred and twenty Th17 cell-specific molecules, twenty-nine were novel cell-surface molecules. Then we revealed that thirteen of them were up-regulated in vivo in inflamed tissues from experimental autoimmune diseases, including spontaneous SKG arthritis, inflammatory bowel disease (IBD) and experimental autoimmune encephalomyelitis (EAE). Next, we analyzed the expression of four membranous molecules, and revealed that podoplanin was expressed highly in the in vitro differentiated Th17 cells. Moreover, at the inflamed synovium of the arthritic SKG mice, most of the accumulating Th17 cells were podoplanin-positive. These results indicate that podoplanin would be a useful Th17 cell marker for diagnosing pathological conditions of autoimmune diseases, including rheumatoid arthritis.

N-cadherin mediates cortical organization in the mouse brain.

The cerebral cortex is a complex laminated structure generated by the sequential migration of developing neurons from the ventricular zone. One of the molecules that may play a role in cortical morphogenesis is N-cadherin since its blocking causes disruption of the ordered arrangement of cells in other neural tissues, such as the neural retina. Here, we show that when the N-cadherin gene had been conditionally deleted in the mouse cerebral cortex, the intra-cortical structures were nearly completely randomized; e.g., mitotic cells and postmitotic cells were scattered throughout the cortex without any order. These defects seemed to mainly originate from the disruption of the adherens junctions (AJs) localized in the apical end of neuroepithelial cells, where N-cadherin is normally most highly concentrated. In the absence of N-cadherin, neuroepithelial or radial glial cells could not expand their bodies or processes to span the distance between the ventricular and pial surfaces and therefore terminated them in the middle zone of the cortex. These results demonstrate that N-cadherin is essential for maintaining the normal architecture of neuroepithelial or radial glial cells and that their disruption randomizes the internal structures of the cortex.