| First Author | Ashbaugh JJ | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 9 | Pages | 4525-34 |
| PubMed ID | 23530149 | Mgi Jnum | J:195519 |
| Mgi Id | MGI:5484712 | Doi | 10.4049/jimmunol.1203214 |
| Citation | Ashbaugh JJ, et al. (2013) IL7Ralpha Contributes to Experimental Autoimmune Encephalomyelitis through Altered T Cell Responses and Nonhematopoietic Cell Lineages. J Immunol 190(9):4525-34 |
| abstractText | A mutation in the IL7Ralpha locus has been identified as a risk factor for multiple sclerosis (MS), a neurodegenerative autoimmune disease characterized by inflammation, demyelination, and axonal damage. IL7Ralpha has well documented roles in lymphocyte development and homeostasis, but its involvement in disease is largely understudied. In this study, we use the experimental autoimmune encephalomyelitis (EAE) model of MS to show that a less severe form of the disease results when IL7Ralpha expression is largely restricted to thymic tissue in IL7RTg(IL7R-/-) mice. Compared with wild-type (WT) mice, IL7RTg(IL7R-/-) mice exhibited reduced paralysis and myelin damage that correlated with dampened effector responses, namely decreased TNF production. Furthermore, treatment of diseased WT mice with neutralizing anti-IL7Ralpha Ab also resulted in significant improvement of EAE. In addition, chimeric mice were generated by bone marrow transplant to limit expression of IL7Ralpha to cells of either hematopoietic or nonhematopoietic origin. Mice lacking IL7Ralpha only on hematopoietic cells develop severe EAE, suggesting that IL7Ralpha expression in the nonhematopoietic compartment contributes to disease. Moreover, novel IL7Ralpha expression was identified on astrocytes and oligodendrocytes endogenous to the CNS. Chimeric mice that lack IL7Ralpha only on nonhematopoietic cells also develop severe EAE, which further supports the role of IL7Ralpha in T cell effector function. Conversely, mice that lack IL7Ralpha throughout both compartments are dramatically protected from disease. Taken together, these data indicate that multiple cell types use IL7Ralpha signaling in the development of EAE, and inhibition of this pathway should be considered as a new therapeutic avenue for MS. |
