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

• Published in: Molecular immunology 2013-06, Vol.54 (2), p.199-207
• Main Authors: Miyamoto, Yoshiaki, Uga, Hitoshi, Tanaka, Satoshi, Kadowaki, Masakazu, Ikeda, Masafumi, Saegusa, Jun, Morinobu, Akio, Kumagai, Shunichi, Kurata, Hirokazu
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Experimental - genetics; Arthritis, Experimental - immunology; Arthritis, Experimental - metabolism; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Cell Differentiation; Cell surface molecules; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - genetics; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Female; Gene Expression Profiling; Gene Expression Regulation; Helper T cell; Immunophenotyping; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - metabolism; Joints - immunology; Joints - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Membrane Proteins - immunology; Membrane Proteins - metabolism; Mice; Rheumatoid arthritis; Th17 Cells - cytology; Th17 Cells - immunology; Th17 Cells - metabolism; Up-Regulation
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2012.11.013

► We improved a Th17 cell differentiation culture and obtained a high purity of Th17 cells. ► Using the Th17 cells, we identified Th17 cell-specific genes by comparative microarray analysis. ► Podoplanin is expressed highly in in vitro differentiated Th17 cells. ► Podoplanin is also expressed highly in joint-infiltrating Th17 cells from SKG arthritic mice. 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.