Upregulation of chemokine receptor expression by IL-10/IL-4 in adult neural stem cells.
It has been shown that adoptively transferred adult neural stem cells (NSCs) ameliorate experimental autoimmune encephalomyelitis (EAE) by differentiating into myelin-forming cells. However, NSC migration into the lesion foci is inefficient and relatively slow, resulting in only modest therapeutic effect. A possible reason for the inefficient migration of NSCs could be the production of anti-inflammatory cytokines by these cells, which might in turn suppress their migration. To address this question we established subventricular zone-derived NSC neurospheres and determined the influence of IL-10 and IL-4 on chemokine receptor expression by these cells, and on their migration in response to chemokines relevant to EAE pathogenesis. We found that treatment with IL-4 and IL-10 upregulates surface adhesion molecule LFA-1 and chemokine receptors CXCR4 and CCR5 on NSCs. IL-10-treated NSCs exhibited significantly higher chemotaxis to the ligands of the above chemokine receptors than untreated cells. Treatment of NSC with IL-4 also resulted in a higher chemotaxis of these cells to RANTES. Thus, in vitro pretreatment with cytokines may be a useful approach to facilitate migration of NSCs into CNS inflammatory foci, producing stronger therapeutic effects. This approach has the potential to improve clinical outcomes of NSC-based therapies for neurological disorders such as multiple sclerosis.
Guan
Yangtai
Y
Department of Neurology, Thomas Jefferson University, 300 JHN Building, 900 Walnut Street, Philadelphia, PA, USA.
Jiang
Zhilong
Z
Ciric
Bogoljub
B
Rostami
A M
AM
Zhang
Guang-Xian
GX
D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002633:Chemotaxis; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D015815:Cell Adhesion Molecules; D019707:Receptors, Chemokine; D016753:Interleukin-10; D015847:Interleukin-4