Grant: Operating Grant

In our pilot study, we showed that rheumatoid arthritis (RA) in mice became worse after they were injected with a molecule called TL1A. This molecule could also increase the production of autoantibody, which is a factor causing arthritis. We further proved that TL1A was produced in human joints. In an attempt to understand how this molecule aggravates arthritis, we generated genetically manipulated mice which do not have the TL1A gene. The objective of this project is to understand how TL1A causes RA. Hypotheses: 1) Local TL1A production in the joints is a part of a vicious circle aggravating RA. 2) In rheumatoid arthritis, TL1A in the spleen and lymph nodes promotes autoantibody production, which is important in causing the disease. Specific aims 1.To assess whether mice lacking the TL1A gene have reduced severity of RA. 2.To study whether TL1A is necessary for inflammation in the joints. 3.To study how TL1A enhances antibody production. Significance This study will address the question whether TL1A is important in RA disease development, and a possible therapeutic target for the disease.