Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3α

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Item Type:	Article
Title:	Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3α
Creators Name:	Lamprecht, B., Kreher, S., Anagnostopoulos, I., Joehrens, K., Monteleone, G., Jundt, F., Stein, H., Janz, M., Doerken, B. and Mathas, S.
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 (gammac) 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 towards HRS cells, which might favour 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.
Keywords:	CD95 Antigens, CD4-Positive T-Lymphocytes, Tumor Cell Line, Cell Lineage, Cell Proliferation, Chemokine CCL20, Neoplastic Gene Expression Regulation, Hodgkin Disease, Immune System, Interleukin-6, Interleukins, STAT3 Transcription Factor, Regulatory T-Lymphocytes, Th2 Cells
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	112
Number:	8
Page Range:	3339-3347
Date:	15 October 2008
Official Publication:	https://doi.org/10.1182/blood-2008-01-134783
PubMed:	View item in PubMed

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