T-cell exhaustion in chronic inflammatory diseases – a scoping review protocol

T cell exhaustion is a distinct state of T cell dysfunction that arises during chronic antigen exposure, including persistent infections, cancer, autoimmunity, and other inflammatory diseases. While this phenomenon is well established in viral infections and cancer, its role in autoimmunity and chronic inflammatory diseases remains poorly defined. Without a comprehensive overview, it remains difficult to determine whether exhaustion mechanisms are shared or disease-specific, to identify biomarkers that reflect disease severity or treatment response, and to evaluate whether therapies targeting exhaustion may have clinical value beyond cancer and infection. By mapping the available evidence, this scoping review aims to clarify how T cell exhaustion is described in different autoimmune and inflammatory diseases, highlight inconsistencies in definitions and methods, and identify disease areas that are understudied. Addressing these knowledge gaps is crucial to guide future mechanistic studies and to support the rational development of new therapeutic strategies for patients with chronic inflammatory conditions.