Study On The Role Of Id3 Gene In T Cell Development And Sj (?) Gren 's Syndrome By Conditional Knockout Mouse Model

The adaptive immune system is critical for the host to defense against foreign pathogens. T and B lymphocytes are the major cellular components of the adaptive immune system. The development and selection of T, B lymphocytes are tightly regulated by genetic network so that they can recognize and attack pathogens and maintain tolerance to self tissues. In this report, we used Id3conditional knockout mouse to study the role of Id3in regulating T cell development and the role of Id3-deficient T cells in the disease development of Sjogren’s syndrome.The Id3gene has been shown to play important roles in the development and function of broad tissue types including B and T cells. Id3deficient mice develop autoimmune disease similar to human Sjogren’s syndrome. Both B and T lymphocytes have been implicated to contribute to the disease phenotype in this disease model. In order to gain a better understanding of individual cell types in this disease model, we generated an Id3conditional allele. An LckCre transgene was used to induce Id3deletion in developing T cells. We showed that the Id3gene was efficiently disrupted in early thymocyte development prior to T cell receptor (TCR)-mediated positive selection. Consequently, thymocyte maturation and selection were impaired in the conditional knockout mice. These mice developed exocrinopathy starting at two months of age and subsequently exhibited high incidence of lymphocyte infiltration to salivary glands between8and12months of age. The progressive features of disease development are very similar to those observed in Id3germline knockout mice. Our results emphasize the cell intrinsic role of Id3in regulating T cell development and indicate that the defects and dysfunction of T development are the major cause of the Sjogren’s syndrome in mice.This study establishes a new model for investigating the relationship between T cell development and autoimmune disease.