Redefining T Cell Pathology in Connective Tissue Disorders: Toward Antigen-Specific Therapies in Systemic Sclerosis and beyond

This thesis explores the role of autoreactive T cells—immune cells that mistakenly attack the body’s own tissues—in autoimmune diseases such as systemic sclerosis (SSc) and other connective tissue diseases (CTDs). These rare cells are difficult to detect, particularly in affected tissues and lymph nodes, but may hold the key to understanding how these diseases develop.

To address this challenge, we developed an innovative toolkit that combines advanced imaging, state-of-the-art molecular techniques, and lab-based functional studies to track and analyze these cells in unprecedented detail.

Our findings reveal that different types of autoreactive T cells play distinct roles in diseases like SSc and Sjögren’s syndrome (SjS). While SjS is primarily driven by helper T cells, SSc appears to be driven by cytotoxic effector T cells. These insights reshape our understanding of the immune system’s role in SSc and open the door to new diagnostic and therapeutic strategies.

Notably, our studies targeting harmful cytotoxic T cells in early-stage SSc patients showed promise in reducing fibrosis—the most debilitating symptom of the disease. This work brings us closer to precision medicine tailored to the unique molecular fingerprints of each autoimmune CTD.