Myeloid cell diversification during regenerative inflammation: Lessons from skeletal muscle

Understanding the mechanisms of tissue and organ regeneration in adult animals and humans is of great interest from a basic biology as well as a medical, therapeutical point of view. It is increasingly clear that the relatively limited ability to regenerate tissues and organs in mammals as oppose to lower vertebrates is the consequence of evolutionary trade-offs and changes during development and aging. Thus, the coordinated interaction of the immune system, particularly the innate part of it, and the injured, degenerated parenchymal tissues such as skeletal muscle, liver, lung, or kidney shape physiological and also pathological processes. In this review, we provide an overview of how morphologically and functionally complete (ad integrum) regeneration is achieved using skeletal muscle as a model. We will review recent advances about the differentiation, activation, and subtype specification of circulating monocyte to resolution or repair-type macrophages during the process we term regenerative inflammation, resulting in complete restoration of skeletal muscle in murine models of toxin-induced injury.