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Journal article
IL7R alpha Contributes to Experimental Autoimmune Encephalomyelitis through Altered T Cell Responses and Nonhematopoietic Cell Lineages
The Journal of immunology (1950), v 190(9), pp 4525-4534
01 May 2013
PMID: 23530149
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A mutation in the IL7R alpha locus has been identified as a risk factor for multiple sclerosis (MS), a neurodegenerative autoimmune disease characterized by inflammation, demyelination, and axonal damage. IL7Ra 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 IL7R alpha 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-IL7R alpha Ab also resulted in significant improvement of EAE. In addition, chimeric mice were generated by bone marrow transplant to limit expression of IL7R alpha to cells of either hematopoietic or nonhematopoietic origin. Mice lacking IL7R alpha only on hematopoietic cells develop severe EAE, suggesting that IL7R alpha expression in the nonhematopoietic compartment contributes to disease. Moreover, novel IL7R alpha expression was identified on astrocytes and oligodendrocytes endogenous to the CNS. Chimeric mice that lack IL7R alpha only on nonhematopoietic cells also develop severe EAE, which further supports the role of IL7R alpha in T cell effector function. Conversely, mice that lack IL7R alpha throughout both compartments are dramatically protected from disease. Taken together, these data indicate that multiple cell types use IL7R alpha signaling in the development of EAE, and inhibition of this pathway should be considered as a new therapeutic avenue for MS. The Journal of Immunology, 2013, 190:4525-4534.
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Details
- Title
- IL7R alpha Contributes to Experimental Autoimmune Encephalomyelitis through Altered T Cell Responses and Nonhematopoietic Cell Lineages
- Creators
- Jessica J. Ashbaugh - University of MiamiRoberta Brambilla - University of MiamiShaffiat A. Karmally - University of MiamiCecilia Cabello - University of MiamiThomas R. Malek - University of MiamiJohn R. Bethea - University of Miami
- Publication Details
- The Journal of immunology (1950), v 190(9), pp 4525-4534
- Publisher
- American Association of Immunologists
- Number of pages
- 10
- Grant note
- 5-R01-NS065479-03; 5-T32-NS007492-08 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Lois Pope LIFE Fellows Program R01NS065479 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Web of Science ID
- WOS:000317907900017
- Scopus ID
- 2-s2.0-84876801098
- Other Identifier
- 991020100064404721
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- Web of Science research areas
- Immunology