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-3 alpha (MIP-3 alpha) inHRScells. MIP-3 alpha 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.

Lamprecht, B., Kreher, S., Anagnostopoulos, I., Johrens, K., Monteleone, G., Jundt, F., et al. (2008). Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts T-reg cells via regulation of MIP-3 alpha. BLOOD, 112(8), 3339-3347 [10.1182/blood-2008-01-134783].

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

MONTELEONE, GIOVANNI;
2008-01-01

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-3 alpha (MIP-3 alpha) inHRScells. MIP-3 alpha 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.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/12 - GASTROENTEROLOGIA
English
Con Impact Factor ISI
CD4 antigen; chemokine receptor CCR6; Fas antigen; interleukin 2 receptor alpha; interleukin 21; interleukin 21 receptor; interleukin 7 receptor; macrophage inflammatory protein 3alpha; STAT3 protein; transcription factor FOXP3; CCL20 protein, human; interleukin 6; interleukin derivative; STAT3 protein, human; apoptosis; article; B lymphocyte; CD4+ CD25+ T lymphocyte; cell protection; controlled study; Hodgkin disease; human; human cell; priority journal; protein expression; Reed Sternberg cell; regulatory T lymphocyte; signal transduction; Th2 cell; upregulation; biosynthesis; CD4+ T lymphocyte; cell lineage; cell proliferation; gene expression regulation; immune system; metabolism; tumor cell line; Antigens, CD95; CD4-Positive T-Lymphocytes; Cell Line, Tumor; Cell Lineage; Cell Proliferation; Chemokine CCL20; Gene Expression Regulation, Neoplastic; Hodgkin Disease; Humans; Immune System; Interleukin-6; Interleukins; STAT3 Transcription Factor; T-Lymphocytes, Regulatory; Th2 Cells
Lamprecht, B., Kreher, S., Anagnostopoulos, I., Johrens, K., Monteleone, G., Jundt, F., et al. (2008). Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts T-reg cells via regulation of MIP-3 alpha. BLOOD, 112(8), 3339-3347 [10.1182/blood-2008-01-134783].
Lamprecht, B; Kreher, S; Anagnostopoulos, I; Johrens, K; Monteleone, G; Jundt, F; Stein, H; Janz, M; Dorken, B; Mathas, S
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/38695
Citazioni
  • ???jsp.display-item.citation.pmc??? 42
  • Scopus 104
  • ???jsp.display-item.citation.isi??? 83
social impact