Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Björn Lamprecht1,2,
  2. Stephan Kreher1,2,
  3. Ioannis Anagnostopoulos3,
  4. Korinna Jöhrens3,
  5. Giovanni Monteleone4,
  6. Franziska Jundt1,2,
  7. Harald Stein3,
  8. Martin Janz1,2,
  9. Bernd Dörken1,2, and
  10. Stephan Mathas1,2
  1. 1Max-Delbrück-Center for Molecular Medicine, Berlin, Germany;
  2. 2Hematology, Oncology and Tumorimmunology, Charité, Medical University Berlin, Berlin, Germany;
  3. 3Institute for Pathology, Charité, Medical University Berlin, Berlin, Germany; and
  4. 4Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy

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+CD127lo 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.

  • Submitted January 18, 2008.
  • Accepted July 21, 2008.
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