Dr. Ming-Zong Lai, a Research Fellow at the Institute of Molecular Biology and his colleagues have discovered that a molecule called "Deltex1" contributes to immune tolerance. Their results, published in the July 17 issue of the highly influential immunology journal "Immunity", are expected to contribute to the future development of immunological therapy. 

Immune tolerance prevents the adaptive immune system (the part of the immune system that develops throughout life) from attacking the body's own tissues. One of the major mechanisms of immune tolerance is the induction of T-cell anergy which prevents T-cell activation. "Anergy" is the term used in immunobiology to describe lack of reaction by the body's defense mechanisms to antigens: so if immune cell anergy is induced, it means that immune cells are not activated and therefore the body’s immunity is compromised.

The molecular processes of T-cell anergy remain incompletely understood among immunologists. Dr. Lai and his group have advanced understanding of these processes by discovering that a molecule called Deltex1 functions to suppress T cell activation. By using transgenic mice, the researchers found that Deltex1 profoundly prevents the activation of T cells. Further study revealed that Deltex1 utilizes at least three distinct mechanisms to prevent T-cell activation: Deltex1 promotes the degradation of a key upstream enzyme (kinase), inactivates another enzyme (kinase), and further targets several biological processes within the cell (signaling cascades). Using these three inhibitory processes, Deltex1 effectively blocks the activation signals in T cells, rendering them inactive. Conversely, if the Deltex1 gene is deleted, T cells become hyper-active. In mice lacking Deltex1, autoantibodies are spontaneously produced, causing inflammation in the lung and liver, indicating that autoimmune diseases are induced in the absence of Deltex1. 

The findings of the research are expected to help in the future development of immunological therapy for the prevention of graft rejection and the elimination of cancer cells.

In addition to his post as researcher at the Institute of Molecular Biology, Dr. Lai is also an Adjunct Professor at Graduate Institute of Microbiology and Immunology, National Yang-Ming University, and an Adjunct Professor at Graduate Institute of Immunology, National Taiwan University. Miss Huey-Wen Hsiao, one of the two co-first authors, is a Ph.D. graduate student at Graduate Institute of Microbiology and Immunology, National Yang-Ming University and Dr. Wen-Hsien Liu, the second co-first author, is a Postdoctoral Fellow at Academia Sinica. The transgenic mouse and knockout mice used in this study were generated in the Academia Sinica Transgenic Mouse Core, with assistance from Dr. Si-Tse Jiang. This study is supported by an Academia Sinica Investigator Award, a National Science Council Frontier Research Grant, and the Institute of Molecular Biology, Academia Sinica.

"Immunity" journal is a highly influential journal in the field of immunology, with an impact factor 20.57. The article entitled "Deltex1 Is a Target of the Transcription Factor NFAT that Promotes T Cell Anergy" Immunity 31, July 17, 2009 can be found at: http://www.cell.com/immunity/abstract/S1074-7613(09)00273-8

The complete list of authors is: Huey-Wen Hsiao, Wen-Hsien Liu, Chen-Jhe Wang, Yu-Hsun Lo, Yung-Hsuan Wu, Si-Tse Jiang and Ming-Zong Lai