Working to seek a better understanding of treatment approaches for rheumatic diseases, creating an environment for rewarding creativity and learning for the next generation of rheumatologists, ultimately improving quality of service and patient outcomes. Learn more.
Translational Rheumatology is focused on the innate and adaptive immune mechanisms that contribute to the onset, progression, persistence and regulation of systemic autoimmune diseases. We pursue excellence in outstanding patient care through innovative research and education for the benefit of people affected by rheumatic diseases. We span the continuum from basic science investigation through to clinical and translational research and clinical trials.
To seeking better understanding treatment approaches for rheumatic diseases, creating an environment for rewarding creativity and learning for the next generation of rheumatologist, ultimately improving quality of service and patient outcomes.
T cell homeostasis in the pathogenesis of Autoimmune Disease
Effective immunologic homeostasis relies on a continual balance in helper T cell activation and regulatory T cell suppression. When homeostasis is disrupted and immune system tips in favor of activation, the host becomes susceptible to autoimmunity. Although it is traditionally believed that many autoimmune are resulted from an aberrant Th1 response via interferon-γ. However, several studies in mice demonstrated the resistance to interferon-γ treatment in autoimmune disorders, which put the role of Th1 lineage in autoimmune pathogenesis into question. Furthermore, discoveries the other T cell subsets (such as Tfh and T17 cells) finally break the long accepted concept about T cells subsets in autoimmunity.
Studies from our group have contributed significantly to the new field of Tfh cells on autoimmune diseases, such as Systemic lupus erythematosus (SLE) or Rheumatoid Arthritis (RA).
- We demonstrated that circulating T follicular helper cells (Tfh cells) in SLE and RA patients shared similar phenotype and functional properties with normal Tfh cells resides on the secondary lymphoid tissue.
- We demonstrated that the accumulated Tfh cells in the peripheral blood and synovial fluid of active SLE and RA patients correlated with the high level of plasmablasts, titer of specific autoantibody, and disease severity in RA and SLE patients.
- Our in vivo experiments showed that purified Tfh cells but not non-Tfh cells from RA patients did support B cells differentiation measured by IgG secretion.
SLE and RA are chronic autoimmune diseases characterized by the production of autoantibodies, binding with self-antigens and potentially causing tissue damage. These high affinity autoantibodies are usually present prior to clinical manifestations, indicating the breakdown of B cell tolerance which causes the expansion of autoreactive B cells and generation of autoreactive plasmablasts. Although there have been many recent advances in the development of therapies for SLE and RA, inadequate responses and therapy resistance are common (30-40%), remission is rarely achieved or sustained. The main root of inadequate or non-responsive outcome is incomplete killing of self-reactive B cells residing in the synovium, B cell-infiltrated tissue, and plasmablasts/plasma cells in the peripheral sites (such as synovium and blood). With the cognate help from T cells, these B cells and plasmablasts are able to survive, expand and differentiate in synovial membranes and the peripheral blood, ultimately produce antibodies and cause tissue/joint damage
Our goal is to address the cellular and molecular basis that permits the survival of autoreactive B cells and the modulation of autoantibody production, and lead to design customized specific therapies targeting foster environment for auto-reactive B cells.
Our Research Programs
- The role of T cell subsets (especially Tfh cells and Th17 cells) in the pathogenesis of SLE and RA.
- Develop specific biological therapy targeting Tfh cells and block auto-antoantibody production in SLE and RA
- Mechanism of cytokines and pathways that regulates both B cell survival, differentiation, and autoimmunity.