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Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3alpha.
- Source :
-
Blood [Blood] 2008 Oct 15; Vol. 112 (8), pp. 3339-47. Date of Electronic Publication: 2008 Aug 06. - Publication Year :
- 2008
-
Abstract
- The malignant Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (HL) are derived from mature B cells, but have lost a considerable part of the B cell-specific gene expression pattern. Consequences of such a lineage infidelity for lymphoma pathogenesis are currently not defined. Here, we report that HRS cells aberrantly express the common cytokine-receptor gamma-chain (gamma(c)) cytokine IL-21, which is usually restricted to a subset of CD4(+) T cells, and the corresponding IL-21 receptor. We demonstrate that IL-21 activates STAT3 in HRS cells, up-regulates STAT3 target genes, and protects HRS cells from CD95 death receptor-induced apoptosis. Furthermore, IL-21 is involved in up-regulation of the CC chemokine macrophage-inflammatory protein-3alpha (MIP-3alpha) in HRS cells. MIP-3alpha in turn attracts CCR6(+)CD4(+)CD25(+)FoxP3(+)CD127(lo) regulatory T cells toward HRS cells, which might favor their immune escape. Together, these data support the concept that aberrant expression of B lineage-inappropriate genes plays an important role for the biology of HL tumor cells.
- Subjects :
- CD4-Positive T-Lymphocytes metabolism
Cell Line, Tumor
Cell Lineage
Cell Proliferation
Humans
Immune System
Interleukin-6 metabolism
fas Receptor biosynthesis
Chemokine CCL20 metabolism
Gene Expression Regulation, Neoplastic
Hodgkin Disease metabolism
Interleukins metabolism
STAT3 Transcription Factor metabolism
T-Lymphocytes, Regulatory metabolism
Th2 Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 112
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 18684866
- Full Text :
- https://doi.org/10.1182/blood-2008-01-134783