Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis

Rachel E. James; James Hillis; István Adorján; Betty Gration; Mayara V. Mundim; Asif J. Iqbal; Moon Moon Majumdar; Richard L. Yates; Maureen M.H. Richards; Gwendolyn E. Goings; Gabriele C. Deluca; David R. Greaves; Stephen D. Miller; Francis G. Szele

doi:10.1002/glia.22906

Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis

Rachel E. James, James Hillis, István Adorján, Betty Gration, Mayara V. Mundim, Asif J. Iqbal, Moon Moon Majumdar, Richard L. Yates, Maureen M.H. Richards, Gwendolyn E. Goings, Gabriele C. Deluca, David R. Greaves, Stephen D. Miller, Francis G. Szele^*

^*Corresponding author for this work

Microbiology-Immunology

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Because MS-induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin-3 (Gal-3), a proinflammatory protein. Gal-3 expression was increased in periventricular regions of human MS in post-mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theiler's murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL, and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal-3^-/- mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal-3^-/- mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal-3^-/- mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal-3 blocked chemokine increases after TMEV, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal-3 plays a central role in modulating the SVZ neurogenic niche's response to this model of MS.

Original language	English (US)
Pages (from-to)	105-121
Number of pages	17
Journal	Glia
Volume	64
Issue number	1
DOIs	https://doi.org/10.1002/glia.22906
State	Published - Jan 1 2016

Funding

NIH; Grant number: RO1NS/AG42253; Grant sponsor: Wellcome Trust Studentship. The authors thank members of the Szele lab for critical reading of the manuscript. They thank Margaret Esiri, Steven Chance, and Daniel Anthony for helpful comments on the project and the manuscript. The authors declare no competing financial interest.

Keywords

Galectin-3
Multiple sclerosis
Subventricular zone

ASJC Scopus subject areas

Neurology
Cellular and Molecular Neuroscience

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10.1002/glia.22906

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James, R. E., Hillis, J., Adorján, I., Gration, B., Mundim, M. V., Iqbal, A. J., Majumdar, M. M., Yates, R. L., Richards, M. M. H., Goings, G. E., Deluca, G. C., Greaves, D. R., Miller, S. D., & Szele, F. G. (2016). Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis. Glia, 64(1), 105-121. https://doi.org/10.1002/glia.22906

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title = "Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis",

abstract = "Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Because MS-induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin-3 (Gal-3), a proinflammatory protein. Gal-3 expression was increased in periventricular regions of human MS in post-mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theiler's murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL, and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal-3-/- mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal-3-/- mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal-3-/- mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal-3 blocked chemokine increases after TMEV, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal-3 plays a central role in modulating the SVZ neurogenic niche's response to this model of MS.",

keywords = "Galectin-3, Multiple sclerosis, Subventricular zone",

author = "James, {Rachel E.} and James Hillis and Istv{\'a}n Adorj{\'a}n and Betty Gration and Mundim, {Mayara V.} and Iqbal, {Asif J.} and Majumdar, {Moon Moon} and Yates, {Richard L.} and Richards, {Maureen M.H.} and Goings, {Gwendolyn E.} and Deluca, {Gabriele C.} and Greaves, {David R.} and Miller, {Stephen D.} and Szele, {Francis G.}",

note = "Publisher Copyright: {\textcopyright} 2015 Wiley Periodicals, Inc.",

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James, RE, Hillis, J, Adorján, I, Gration, B, Mundim, MV, Iqbal, AJ, Majumdar, MM, Yates, RL, Richards, MMH, Goings, GE, Deluca, GC, Greaves, DR, Miller, SD & Szele, FG 2016, 'Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis', Glia, vol. 64, no. 1, pp. 105-121. https://doi.org/10.1002/glia.22906

TY - JOUR

T1 - Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis

AU - James, Rachel E.

AU - Hillis, James

AU - Adorján, István

AU - Gration, Betty

AU - Mundim, Mayara V.

AU - Iqbal, Asif J.

AU - Majumdar, Moon Moon

AU - Yates, Richard L.

AU - Richards, Maureen M.H.

AU - Goings, Gwendolyn E.

AU - Deluca, Gabriele C.

AU - Greaves, David R.

AU - Miller, Stephen D.

AU - Szele, Francis G.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Because MS-induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin-3 (Gal-3), a proinflammatory protein. Gal-3 expression was increased in periventricular regions of human MS in post-mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theiler's murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL, and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal-3-/- mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal-3-/- mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal-3-/- mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal-3 blocked chemokine increases after TMEV, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal-3 plays a central role in modulating the SVZ neurogenic niche's response to this model of MS.

AB - Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Because MS-induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin-3 (Gal-3), a proinflammatory protein. Gal-3 expression was increased in periventricular regions of human MS in post-mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theiler's murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL, and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal-3-/- mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal-3-/- mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal-3-/- mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal-3 blocked chemokine increases after TMEV, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal-3 plays a central role in modulating the SVZ neurogenic niche's response to this model of MS.

KW - Galectin-3

KW - Multiple sclerosis

KW - Subventricular zone

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Loss of galectin-3 decreases the number of immune cells in the subventricular zone and restores proliferation in a viral model of multiple sclerosis

Abstract

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