| First Author | Liu T | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 2 | Pages | 113721 |
| PubMed ID | 38310514 | Mgi Jnum | J:350590 |
| Mgi Id | MGI:7613969 | Doi | 10.1016/j.celrep.2024.113721 |
| Citation | Liu T, et al. (2024) An axon-T cell feedback loop enhances inflammation and axon degeneration. Cell Rep 43(2):113721 |
| abstractText | Inflammation is closely associated with many neurodegenerative disorders. Yet, whether inflammation causes, exacerbates, or responds to neurodegeneration has been challenging to define because the two processes are so closely linked. Here, we disentangle inflammation from the axon damage it causes by individually blocking cytotoxic T cell function and axon degeneration. We model inflammatory damage in mouse skin, a barrier tissue that, despite frequent inflammation, must maintain proper functioning of a dense array of axon terminals. We show that sympathetic axons modulate skin inflammation through release of norepinephrine, which suppresses activation of gammadelta T cells via the beta2 adrenergic receptor. Strong inflammatory stimulation-modeled by application of the Toll-like receptor 7 agonist imiquimod-causes progressive gammadelta T cell-mediated, Sarm1-dependent loss of these immunosuppressive sympathetic axons. This removes a physiological brake on T cells, initiating a positive feedback loop of enhanced inflammation and further axon damage. |
