Skeletal muscle accounts for a large fraction of body mass and serves as both the effector of movement and a key regulator of organismal metabolism. Although parenchymal cells perform the core functions of skeletal muscle (e.g., contractile, metabolic, and endocrine functions), tissue homeostasis is supported by the activities of various non-parenchymal cell types, including mesenchymal stromal cells and leukocytes. Exercise, injury, and aging are common forms of stress imposed on skeletal muscle. Adaptation to these challenges is regulated by the immune system; however, the underlying cellular and molecular mechanisms remain unclear. Dissecting the immunobiology of skeletal muscle in these contexts is methodologically demanding, as it requires an interdisciplinary approach that draws on cellular immunology, exercise physiology, tissue biomechanics, and bioenergetics.

This Topical Collection assembles rigorous, reproducible protocols spanning these and other disciplines and presents them through detailed visual demonstrations, making each specialized technique accessible to investigators trained in adjacent fields. With this integrated toolbox, researchers will be equipped with the methods needed to uncover new insights into the immunobiology of skeletal muscle in the contexts of exercise, injury, and aging. Such work will inform the development of interventions to enhance performance, improve regeneration and function after injury, reduce the burden of musculoskeletal diseases, and combat age-related frailty.