Repairing a tissue after an injury requires the infiltration of inflammatory cells and the activation of the resident stem cells, which will restore the damaged tissue. But for full tissue recovery to happen, the inflammation that is first necessary must be resolved. The Myogenesis research group at the CEXS-UPF, led by Pura Muñoz-Cánoves, has recently provided evidence of how this happens.
For the inflammation to disappear, macrophages (a type of immune cells that are involved in the healing of muscle and other tissues) must switch from a pro-inflammatory to an anti-inflammatory phenotype. While it is known that disturbing the interactions between inflammatory cells and tissue resident cells prevents successful healing, the molecular mechanisms underlying the interactions between these cell types are practically unknown.
In an Extra Views article recently published in Cell Cycle, the authors review their work about how macrophages control stem cell-dependent tissue repair. In particular, Muñoz-Cánoves and colleagues demonstrated, in a paper in Journal of Cell Biology, a new function for MAPK phosphatase MKP-1 (MKP-1) in the regulation of p38 MAPK (p38) signaling, which leads to the deactivation of macrophages during inflammation resolution after injury.
At advanced stages of regeneration, MKP-1 loss caused an unscheduled “exhaustion-like” state in muscle macrophages, in which neither pro- nor anti-inflammatory cytokines are expressed despite persistent tissue damage. This leads to reparation by the tissue stem cells.
Because this progressive attenuation of pro-inflammatory gene expression is also involved in the process of tolerance to bacterial infection, the authors discuss the potential similarities between the two mechanisms: inflammation resolution during tissue repair (studied in this work) and endotoxin tolerance.
Perdiguero E, Sousa-Victor P, Ruiz-Bonilla V, Jardí M, Caelles C, Serrano AL, Muñoz-Cánoves P
p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair.
J Cell Biol. 2011 Oct 17;195(2):307-22