| First Author | Khaw YM | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 105 |
| PubMed ID | 33397973 | Mgi Jnum | J:301166 |
| Mgi Id | MGI:6502930 | Doi | 10.1038/s41467-020-20302-0 |
| Citation | Khaw YM, et al. (2021) Early-life-trauma triggers interferon-beta resistance and neurodegeneration in a multiple sclerosis model via downregulated beta1-adrenergic signaling. Nat Commun 12(1):105 |
| abstractText | Environmental triggers have important functions in multiple sclerosis (MS) susceptibility, phenotype, and trajectory. Exposure to early life trauma (ELT) has been associated with higher relapse rates in MS patients; however, the underlying mechanisms are not well-defined. Here we show ELT induces mechanistic and phenotypical alterations during experimental autoimmune encephalitis (EAE). ELT sustains downregulation of immune cell adrenergic receptors, which can be attributed to chronic norepinephrine circulation. ELT-subjected mice exhibit interferon-beta resistance and neurodegeneration driven by lymphotoxin and CXCR2 involvement. These phenotypic changes are observed in control EAE mice treated with beta1 adrenergic receptor antagonist. Conversely, beta1 adrenergic receptor agonist treatment to ELT mice abrogates phenotype changes via restoration of immune cell beta1 adrenergic receptor function. Our results indicate that ELT alters EAE phenotype via downregulation of beta1 adrenergic signaling in immune cells. These results have implications for the effect of environmental factors in provoking disease heterogeneity and might enable prediction of long-term outcomes in MS. |
