Lactate Signalling Plays Key Role in Aggregation of Immune-Inflammatory Hotspots in Autoimmune Diseases

Researchers at the University of Birmingham have made a groundbreaking discovery in the field of immunology, revealing that lactate signalling plays a crucial role in the aggregation of immune-inflammatory hotspots in autoimmune diseases. According to their study, published in Nature Metabolism, lactate is a master regulator of ectopic lymphoid structures (ELS) organization in Sjögren's disease, a common autoimmune rheumatic disease. The team has identified a previously unappreciated checkpoint in autoimmune inflammatory diseases, which can be targeted to promote resolution.

Key Takeaways:

• Ectopic lymphoid structures (ELS) are aggregates of lymphoid cells that form within inflamed tissues in patients with autoimmune diseases, cancer, infectious diseases, and cardiovascular conditions.
• Lactate signalling is a key regulator of ELS organization in Sjögren's disease, the second-most common autoimmune rheumatic disease.
• Inhibiting lactate uptake by lactate transporters, specifically by SLC5A12 blockade, represents a previously unappreciated checkpoint in autoimmune inflammatory diseases.
• This approach results in multidimensional pro-resolution effects, including reduced inflammatory cytokine levels, enhanced T cell egress from inflamed sites, and diminished T cell and B cell areas and their segregation within ELS.
• The study has been peer-reviewed and published in Nature Metabolism.

Statistics:

• The study involved researchers from the University of Birmingham, including Michelangelo Certo, Jason D. Turner, Charlotte G. Smith, Joana Campos, Saba Nayar, Benjamin A. Fisher, Claudio Mauro, Elena Pontarini, Davide Lucchesi, Daria Apostolo, Michele Bombardieri, Sebastian G. Gilbert, Fabian Spill, Ronny Schmidt, Christoph Schroeder, Giulia Cavallaro, and Serena Colafrancesco.
• Funding for the research came from the Medical Research Council UK (MRC), University of Birmingham Professorial Fellowship, British Heart Foundation Senior Basic Science Research Fellowship, British Sjögren's Syndrome Association, Barts Charity Seed Grant for Research, Versus Arthritis, National Institute for Health and Care Research (NIHR) Musculoskeletal Biomedical Research Centre, and others.
• The study was published in Nature Metabolism, a peer-reviewed journal.

Sources:

• Lactate Signalling Leads To Aggregation of Immune-inflammatory Hotspots and Slc5a12 Blockade Promotes Their Resolution. Nature Metabolism, 2025;7(8):1663-1680.
• NewsRx. Investigators at University of Birmingham Report Findings in Autoimmunity (Lactate Signalling Leads To Aggregation of Immune-inflammatory Hotspots and Slc5a12 Blockade Promotes Their Resolution). Health & Medicine Week. October 31, 2025; p 2150.