Functional capability of IL-15-Akt signaling in the denervated muscle

Denervation of skeletal muscles results in timely muscle-T cell cross-talk, but the mechanistic details of the orchestrated local circuits, as well as the potential regulatory link to the muscular function have not been established.

We used a combination of techniques to measure: (i) timely expression of IL-1β-ERK1/2 and IL-15-Akt signaling and (ii) cellular events controlled by IL-15-Akt signaling. Techniques included gastrocnemius strip, satellite cell culture, real time PCR, immunoprecipitation, Western blotting and subcellular fractionation. Besides that, muscle cell survival was determined by MTT assay.

We found that there were two events: rapid IL-1β-ERK1/2 (1 day) and the later IL-15-Akt signaling (7 day) were selectively triggered by sciatic nerve injury. IL-15-Akt signaling was mostly targeted on CD2 phosphorylation and strengthened CD2-CD48 adhesion within gastrocnemius lipid rafts, in the same time, it exerted a restriction on TAB2 via miR155 pathway, thereby prevented muscle cell from inflammatory damage.

Our results suggested that IL-15-Akt signaling harbored the complex signals for muscle-T cell interaction, the regulatory networks have significant potential for the restriction on IL-1β inflammatory signaling. These results are likely to provide new insights into the therapy of neuromuscular injury.