In:
The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 1_Supplement ( 2011-04-01), p. 164.7-164.7
Abstract:
Th17 cells play a critical role in the pathogenesis of several autoimmune and inflammatory diseases. Intravenous immunoglobulin (IVIg), a therapeutic preparation of polyclonal IgG, increasingly used in the treatment of diverse autoimmune and inflammatory diseases, may target Th17 cells to exert therapeutic effects. Therefore, we examined whether IVIg interferes with the development and function of human Th17 cells. To address this, Th17 cells were differentiated from naïve human CD4+ T cells in the presence of TGFβ and IL-21. Th17 cells were amplified by stimulating memory CD4+ T cells in the presence of IL-1β and IL-6. The effect of IVIg was examined on differentiation and amplification of Th17 cells, expression of Th17 lineage-specific transcription factor RORC, secretion of Th17 effector cytokines and phosphorylation of STAT3, a transcription factor that plays an important role in Th17 development and function. IVIg inhibits the differentiation and amplification of human Th17 cells, as well as the production of their effector cytokines IL-17A, IL-17F, IL-21 and CCL20. The inhibitory effects of IVIg on Th17 cells are F(ab')2-dependent and involve interference with the expression of RORC and activation of STAT3. Also, IVIg significantly enhanced Foxp3+ regulatory T cells (Treg) among the memory CD4+ T cells. These results reveal a novel mechanism of action of IVIg in achieving therapeutic effect in autoimmune and inflammatory diseases.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.186.Supp.164.7
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2011
detail.hit.zdb_id:
1475085-5
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