| First Author | Wu J | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 24 | Pages | eaba3458 |
| PubMed ID | 32582853 | Mgi Jnum | J:291158 |
| Mgi Id | MGI:6444927 | Doi | 10.1126/sciadv.aba3458 |
| Citation | Wu J, et al. (2020) Skeletal muscle antagonizes antiviral CD8(+) T cell exhaustion. Sci Adv 6(24):eaba3458 |
| abstractText | CD8(+) T cells become functionally impaired or "exhausted" in chronic infections, accompanied by unwanted body weight reduction and muscle mass loss. Whether muscle regulates T cell exhaustion remains incompletely understood. We report that mouse skeletal muscle increased interleukin (IL)-15 production during LCMV clone 13 chronic infection. Muscle-specific ablation of Il15 enhanced the CD8(+) T cell exhaustion phenotype. Muscle-derived IL-15 was required to maintain a population of CD8(+)CD103(+) muscle-infiltrating lymphocytes (MILs). MILs resided in a less inflamed microenvironment, expressed more T cell factor 1 (Tcf1), and had higher proliferative potential than splenic T cells. MILs differentiated into functional effector T cells after reentering lymphoid tissues. Increasing muscle mass via muscle-specific inhibition of TGFbeta signaling enhanced IL-15 production and antiviral CD8(+) T cell responses. We conclude that skeletal muscle antagonizes T cell exhaustion by protecting T cell proliferative potential from inflammation and replenishing the effector T cell progeny pool in lymphoid organs. |
