Hideki Ueno, M.D., Ph.D.

Baylor Research Institute, Houston, TX

2015 Cell Signaling, Target Identification, T Cells, Human Lupus Biology, Immune System Function

2015 Blocking Newly Discovered Signal to Slow Down Lupus

The Study and What it Means to Patients

Recent studies show that immune cells called T follicular helper cells help drive the lupus immune system to attack. We have discovered a specific protein that signals to T cells and promotes their development into T follicular helper cells.  Our team will investigate if blocking the signal eliminate or inhibit these dangerous T cells. With this information, we will have a better understanding of what contributes to autoimmunity in lupus.


T follicular helper cells are immune cells that support the development of antibody responses. In lupus, these T cells don’t function as they normally would, which leads to production of antibodies that attack rather than protect the body’s organs and tissues. With our Novel Research Grant, we are exploring how and why the specific protein communicates with T cells to cause them to function abnormally in lupus. With more information on this signal and its effects, we hope to one day translate our findings into the clinic to design medicines that can inhibit T follicular helper cells. Eventually, this research could yield a potential new treatment option for autoimmune diseases, including lupus.

Scientific Abstract: A new disease mechanism in lupus

Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory autoimmune disease characterized by a breakdown of tolerance to nuclear antigens. Mouse studies with lupus models have demonstrated that T follicular helper (Tfh) cells play a major pathogenic role in lupus, and inhibition of the generation and/or activity of Tfh cells is beneficial for disease prevention and treatment. Supporting evidence was also obtained in studies of human SLE. However, little is known regarding the mechanism involved in aberrant Tfh responses in SLE.  Our recent study shows that a TNF ligand family molecule expressed by myeloid APCs contributes to the aberrant Tfh response in SLE and therefore provides a rationale to block this axis as a therapeutic and/or preventive strategy for SLE. However, much remains to be determined to bring this concept into the clinic. The three aims in this study are:  AIM 1: To identify molecular mechanisms by which  signaling through the specific molecule induces the expression of Tfh molecules by human Th cells. AIM 2: To identify the range of immune cells expressing the specific molecule at inflamed tissues in SLE. AIM 3: To determine the role of the immune complex for the expression of the specific molecule. Our study will establish how this novel mechanism contributes to lupus pathogenesis.