J Immunol. 2003 Jul 15;171(2):616-627
Kim H, Suh JM, Hwang ES, Kim DW, Chung HK, Song JH, Hwang JH, Park KC, Ro HK, Jo EK, Chang JS, Lee TH, Lee MS, Kohn LD, Shong M.
Laboratory of Endocrine Cell Biology, Department of Internal Medicine, Department of Microbiology and Immunology, Chungnam National University School of Medicine, Daejon, Korea. Department of Biology, Daejin University, Kyeonggido, Korea. Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Department of Biomedical Sciences, Ohio University School of Osteopathic Medicine and Edison Biotechnology Institute, Athens, OH 45701.
It has been suggested that class I and class II MHC are contributing factors for numerous diseases including autoimmune thyroid diseases, type 1 diabetes, rheumatoid arthritis, Alzheimer's disease, and multiple sclerosis.
The class II trans-activator (CIITA), which is a non-DNA-binding regulator of class II MHC transcription, regulates the constitutive and inducible expression of the class I and class II genes.
FRTL-5 thyroid cells incubated in the presence of IFN-gamma have a significantly higher level of cell surface rat MHC class II RTI.B.
However, the IFN-gamma-induced RT1.B expression was suppressed significantly in cells incubated in the presence of thyrotropin.
Thyrotropin (TSH) represses IFN-gamma-induced CIITA expression by inhibiting type IV CIITA promoter activity through the suppression of STAT1 activation and IFN regulatory factor 1 induction.
This study found that TSH induces transcriptional activation of the STAT3 gene through the phosphorylation of STAT3 and CREB activation.
TSH induces SOCS-1 and SOCS-3, and TSH-mediated SOCS-3 induction was dependent on STAT3.
The cell line stably expressing the wild-type STAT3 showed a higher CIITA induction in response to IFN-gamma and also exhibited TSH repression of the IFN-gamma-mediated induction of CIITA.
However, TSH repression of the IFN-gamma-induced CIITA expression was not observed in FRTL-5 thyroid cells, which stably expresses the dominant negative forms of STAT3, STAT3-Y705F, and STAT3-S727A.
This report suggests that TSH is also engaged in immunomodulation through signal cross-talk with the cytokines in thyroid cells.