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Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Tregcells via regulation of MIP-3α
- Source :
- Blood; October 2008, Vol. 112 Issue: 8 p3339-3347, 9p
- 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 γ-chain (γc) 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-3α (MIP-3α) in HRS cells. MIP-3α in turn attracts CCR6+CD4+CD25+FoxP3+CD127loregulatory 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.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 112
- Issue :
- 8
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs56988778
- Full Text :
- https://doi.org/10.1182/blood-2008-01-134783