Hepcidin messenger RNA expression in human lymphocytes

Immunology. 2010 Jun;130(2):217-30. doi: 10.1111/j.1365-2567.2009.03226.x. Epub 2010 Jan 19.


Hepcidin regulates intracellular iron levels by interacting with and promoting the degradation of ferroportin, a membrane protein and the only known cellular iron exporter. Studies of hepcidin expression and regulation have focused on its effects in innate immunity and as a regulator of systemic iron metabolism. In the present study we characterized the expression of hepcidin messenger RNA (mRNA) in human peripheral blood mononuclear cells (PBMCs) with a focus on peripheral blood lymphocytes (PBLs). We found that (1) all human PBMCs analyzed express basal hepcidin mRNA levels; (2) hepcidin mRNA expression increases after T-lymphocyte activation; (3) expression by PBLs increases in response to challenge by holotransferrin (Fe-TF) and by ferric citrate in vitro; (4) the Fe-TF-mediated up-regulation of hepcidin decreases ferroportin expression at the cytoplasmic membrane of PBLs; and (5) silencing of tumour necrosis factor-alpha (TNF-alpha) abrogates the effect of Fe-TF. In summary, we show that hepcidin expression determines intracellular iron levels by regulating the expression of ferroportin, as described in other cells, and that inappropriately low expression of hepcidin impairs normal lymphocyte proliferation. The results establish hepcidin as a new player in lymphocyte biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimicrobial Cationic Peptides / biosynthesis
  • Antimicrobial Cationic Peptides / immunology*
  • Cation Transport Proteins / biosynthesis
  • Cation Transport Proteins / immunology
  • Cell Proliferation / drug effects
  • Female
  • Ferric Compounds / pharmacology
  • Gene Silencing / drug effects
  • Gene Silencing / immunology
  • Hepcidins
  • Humans
  • Immunity, Innate / physiology
  • Iron / immunology
  • Iron / metabolism
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transferrin / immunology
  • Transferrin / metabolism
  • Transferrin / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology
  • Up-Regulation / drug effects
  • Up-Regulation / immunology*


  • Antimicrobial Cationic Peptides
  • Cation Transport Proteins
  • Ferric Compounds
  • HAMP protein, human
  • Hepcidins
  • RNA, Messenger
  • Transferrin
  • Tumor Necrosis Factor-alpha
  • holotransferrin
  • metal transporting protein 1
  • ferric citrate
  • Iron