Genes from thymic epithelaium to Tumor Immunology

초록

Genes from Thymic Epithelium to Tumor Immunology A journey began when my mission as a postdoc focused on hunting for new genes from the thymic epithelial cells (TEC) in NIH (Ronald H. Schwartz’s lab). One particular gene fished out from PCR based subtractive library was named as Thymic Stromal Co transporter (also named as Ly110 by Jackson Laboratory, later officially called as Slc46a) since its expression appeared limited in the cortical thymic epithelilal cells. Although its specific biological function is still unknown, expression of this gene lead a new window to study the differentiation process and the roles of thymic epithelial cells. We initially approached a question (a dogma at the time) with lacZ knock in mouse model if thymic cortical epithelium was excluded from the negative selection to a specific antigen expressed in the cortical epithelium. We found surprising efficiency of negative selection without cross presentation. Currently we have multiple mouse models uniquely expressing reporter EGFP, nitroreductase for inducible TEC cell ablation, or Cre for the conditional manipulation of any gens in TEC under the control of TSCOT promoter. We used these lines to test gamma delta T cell development and TEC lineage specification and compartmentalization. Another gene from the same library was named as epithin (for epithelia trypsin like protease) is a membrane type II serine protease (named as PRSS14 by Jackson) and became my pet molecule for the current research in the field of tumor immunology. Its expression is highly upregulated in nearly all, if not all, advanced epithelial cancers. It can be induced in the activated macrophage through JAK/Stat1 pathway. It showed interesting functions in angiogenesis, EMT, transendothelial migration, and mestastasis in our studies. We are now asking immunological questions using epithin as a metastasis marker and a model antigen: Can we make preventive metastasis va