The Role of T Lymphocytes in Skeletal Muscle Repair From Traumatic and Contraction-Induced Injury

Abstract

Skeletal muscle is prone to damage from a range of stimuli, and initiates a robust repair process that requires the participation of immune cells. Among the more well characterized immune cells involved in muscle repair are those of the myeloid lineage, including neutrophils, macrophages, monocytes, and eosinophils. More recently, studies have begun to elucidate the role of the lymphoid-derived immune cells, most notably T lymphocytes (T-cells), in the complex processes of muscle repair. Though T-cells have been traditionally been associated with pathological degeneration of skeletal muscle in disease, recent studies show that T-cells are instrumental in the repair/regeneration process following severe muscle damage in mice. Furthermore, a few studies using basic immunohistochemical assays have shown that T-cells accumulate in human skeletal muscle in the days following contraction-induced muscle damage. The functional significance of T-cells in the repair and adaptation process following contraction-induce muscle damage remains uncertain, and is an active area of intense investigation. This mini-review summarizes recent findings on the involvement of T-cells in skeletal muscle repair.

Keywords: T-cell; Treg; exercise; inflammation; lymphoid; muscle damage; muscle regeneration; satellite cell.

FIGURE 1

Schematic summary of the known mechanisms by which T-cells support muscle regeneration and recovery from traumatic injury. CD8+ T-cells facilitate CCL2 expression by muscle resident macrophages, which is essential for the recruitment of pro-inflammatory monocytes to the injured muscle. In the absence of CD8+ T-cells, pro-inflammatory monocyte recruitment is blunted, satellite cell pool is reduced, nascent myofiber growth is attenuated, and matrix deposition is exacerbated (see Zhang et al., 2014). Regulatory T (Treg) cells support muscle regeneration in part by the growth factor amphiregulin (AREG). Muscle Tregs express high levels of AREG. AREG treatment normalized the evolution of the muscle transcriptome over the course of the muscle repair process, and promotes myogenic differentiation in vitro (Burzyn et al., 2013). Muscle lacking or deficient in Tregs following injury suffer from exaggerated extracellular matrix deposition, slowed nascent fiber growth, and exaggerated inflammation, and failure of M1 macrophages to mature into M2 macrophages (Burzyn et al., 2013; Kuswanto et al., 2016). CCL2; C-C motif chemokine ligand 2; SC; satellite cell; WBC; white blood cell.