The role of IL-32 in cutaneous T-cell lymphoma

J Invest Dermatol. 2014 May;134(5):1428-1435. doi: 10.1038/jid.2013.488. Epub 2013 Nov 13.

Abstract

IL-32 is a pro-inflammatory cytokine expressed by activated natural killer cells, T cells, keratinocytes, and fibroblasts. In this study, we examined the role of IL-32 in cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF) and Sézary syndrome (SS). IL-32 mRNA expression levels in lesional skin of MF patch, plaque, and tumor were increased compared with those of normal skin, which positively correlated with CCL17 and CCL18 mRNA expression levels. Serum IL-32 levels positively correlated with disease activity within each patient. Immunostaining showed that keratinocytes expressed IL-32 in the lesional skin of MF patch and plaque, whereas in MF tumor, atypical T cells in the dermis strongly expressed IL-32. We also showed that IL-32 dose-dependently accelerated the proliferation of MF and SS cell lines in vitro, which was inhibited by blocking mitogen-activated protein kinase and NF-κB-mediated signaling. The addition of anti-IL-32 antibodies in culture decreased the proliferation of SS cells and the viability of MF cells, suggesting that IL-32 serves as an autocrine growth factor. In conclusion, our results suggest that IL-32 has a role in the formation and maintenance of CTCL lesions, providing a possible therapeutic target for patients with this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Proliferation
  • Chemokine CCL17 / genetics
  • Chemokine CCL17 / immunology
  • Chemokines, CC / genetics
  • Chemokines, CC / immunology
  • Female
  • Humans
  • Interleukins / blood
  • Interleukins / genetics*
  • Interleukins / immunology*
  • Lymphoma, T-Cell, Cutaneous / genetics*
  • Lymphoma, T-Cell, Cutaneous / immunology*
  • Lymphoma, T-Cell, Cutaneous / metabolism
  • MAP Kinase Signaling System / immunology
  • Male
  • Middle Aged
  • Mycosis Fungoides / genetics
  • Mycosis Fungoides / immunology
  • Mycosis Fungoides / metabolism
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • Sezary Syndrome / genetics
  • Sezary Syndrome / immunology
  • Sezary Syndrome / metabolism
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / metabolism

Substances

  • CCL17 protein, human
  • CCL18 protein, human
  • Chemokine CCL17
  • Chemokines, CC
  • IL32 protein, human
  • Interleukins
  • NF-kappa B
  • RNA, Messenger