In:
The Journal of Immunology, The American Association of Immunologists, Vol. 183, No. 1 ( 2009-07-01), p. 246-253
Abstract:
Th17 and Th1 play an important role in multiple sclerosis for which copolymer I (COP-I) is a treatment option. We described here that the treatment effect of COP-I correlated with its unique regulatory properties on differentiation and survival of Th17 in experimental autoimmune encephalomyelitis mice, which was mediated through down-regulation of STAT3 phosphorylation. The effect of COP-I on Th17 differentiation required CD14+ monocytes through IL-6 signaling as a key mediator to regulate STAT3 phosphorylation and subsequent RORγt expression in Th17 cells. The observed effect was markedly dampened when monocytes were genetically deficient for IL-6. Similar regulatory properties of COP-I were demonstrated in human Th17 differentiation. The study revealed the differential regulatory roles and the novel mechanism of action of COP-I chiefly responsible for its treatment efficacy in experimental autoimmune encephalomyelitis and multiple sclerosis.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.0900193
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2009
detail.hit.zdb_id:
1475085-5
