Local breach of tolerance – understanding the process of chronicity in autoimmune disease

Introduction | Chronic inflammation in autoimmune diseases is driven by resident T cells and a breakdown in immune tolerance. Systemic factors often complicate the study of local antigen presentation; however, juvenile idiopathic arthritis (JIA) provides a unique model due to its joint-specific inflammation. While innate immune-driven T-cell activation has been observed in JIA, the roles of autoantibodies and autoreactive lymphocytes remain unclear. Mapping these factors will improve understanding of local tolerance breakdown and support the development of targeted therapies and patient subgroup identification in autoimmune diseases.

Aim | To investigate the mechanisms of local tolerance breach by identifying autoantigens, autoantibodies, and autoreactive lymphocytes.

Methods | We propose that lymphocytes migrate to joints and target local autoantigens, leading to immune activation and a breach of tolerance. To explore this, we aim to identify autoantigens and autoreactive lymphocytes, uncovering mechanisms of activation and their potential as therapeutic targets.

Significance | Local breaches of tolerance play a key role in autoimmune diseases, but systemic influences make them difficult to study. Using JIA as a model with minimal systemic involvement, we seek to identify key immune components involved in disease progression. Our findings will provide insights into localized autoimmunity, refine patient classification, and guide targeted therapies. This approach may also be applicable to other autoimmune diseases, such as diabetes and inflammatory bowel disease, offering novel strategies for personalized diagnosis and treatment.

IGNITE Fellow - Elisabeth Bankell 

Elisabeth Bankell has a background in Molecular Biology from the Faculty of Science at Lund University. Before earning her Master’s degree, she spent a year abroad as an exchange student at Nanyang Technological University (NTU) in Singapore. 

She holds a PhD in Medical Science from Lund University, where her research focused on innate immunity and inflammatory signaling. During her doctoral work, she investigated how the antimicrobial peptide LL-37 can induce apoptosis in host cells, and how myocardin-related transcription factors (MRTFs) in vascular smooth muscle cells exert anti-inflammatory effects. Since elevated levels of LL-37 have been linked to several autoimmune and inflammatory diseases, and the role of smooth muscle cells in regulating vascular inflammation remains poorly understood, her findings contribute to a broader understanding of how innate immune mechanisms influence chronic inflammatory diseases such as atherosclerosis. 

As an IGNITE fellow, Elisabeth joins Robin Kahn’s group to investigate the mechanisms underlying the local breach of tolerance in autoimmune disease, using juvenile idiopathic arthritis (JIA) as a model. Her project aims to identify autoantigens, autoantibodies, and autoreactive lymphocytes involved in local autoimmune reactions. By characterizing these factors and their interplay, the goal is to pinpoint specific mechanisms and patterns that could be targeted for therapy, ultimately contributing to a better understanding of chronicity in autoimmune diseases. 

Main Principal Investigator

• Robin Kahn

Co-supervisors

• Anders Bengtsson         
• Pontus Nordenfelt