Medeea Badii1, Orsolya Gaal1, Radu A Popp2, Tania O Crișan2, Leo A B Joosten3. 1. Department of Medical Genetics, "Iuliu Hațieganu" University of Medicine and Pharmacy, Str. Pasteur nr. 6, 400349, Cluj-Napoca, Romania; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, The Netherlands; Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands. 2. Department of Medical Genetics, "Iuliu Hațieganu" University of Medicine and Pharmacy, Str. Pasteur nr. 6, 400349, Cluj-Napoca, Romania. 3. Department of Medical Genetics, "Iuliu Hațieganu" University of Medicine and Pharmacy, Str. Pasteur nr. 6, 400349, Cluj-Napoca, Romania; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, The Netherlands; Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands. Electronic address: leo.joosten@radboudumc.nl.
Abstract
BACKGROUND: Rheumatic diseases include a variety of autoimmune and autoinflammatory conditions that are characterised by musculoskeletal involvement and systemic disease. Both innate and adaptive immunity can contribute to the complex inflammatory processes that take part in the pathogenesis of these debilitating disorders. FINDINGS: Over the past decade, studies have led to a paradigm-shift around the concept of immune memory, generating the knowledge that cells of the innate immune system can develop a de facto memory mediated by epigenetic reprograming and metabolic changes (trained immunity). Here we provide an overview of current data that describe features of trained immunity in rheumatic diseases. We link evidence on inflammatory mediators and cytokine production, immunometabolism and epigenetic regulation of immunological programs, and outline the fact that trained immunity could play mechanistic roles in rheumatic diseases such as gout, rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis. CONCLUSION: This review describes recent findings in several important rheumatic disorders and emphasizes changes in the functional program of innate immune cells that are reminiscent of a trained immune phenotype. Further assessment of trained immunity in rheumatic disease can provide targetable mechanisms that could potentially alter the disease symptomatology and evolution.
BACKGROUND: Rheumatic diseases include a variety of autoimmune and autoinflammatory conditions that are characterised by musculoskeletal involvement and systemic disease. Both innate and adaptive immunity can contribute to the complex inflammatory processes that take part in the pathogenesis of these debilitating disorders. FINDINGS: Over the past decade, studies have led to a paradigm-shift around the concept of immune memory, generating the knowledge that cells of the innate immune system can develop a de facto memory mediated by epigenetic reprograming and metabolic changes (trained immunity). Here we provide an overview of current data that describe features of trained immunity in rheumatic diseases. We link evidence on inflammatory mediators and cytokine production, immunometabolism and epigenetic regulation of immunological programs, and outline the fact that trained immunity could play mechanistic roles in rheumatic diseases such as gout, rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis. CONCLUSION: This review describes recent findings in several important rheumatic disorders and emphasizes changes in the functional program of innate immune cells that are reminiscent of a trained immune phenotype. Further assessment of trained immunity in rheumatic disease can provide targetable mechanisms that could potentially alter the disease symptomatology and evolution.