VEN-120, a Recombinant Human Lactoferrin, Promotes a Regulatory T Cell [Treg] Phenotype and Drives Resolution of Inflammation in Distinct Murine Models of Inflammatory Bowel Disease

J Crohns Colitis. 2017 Sep 1;11(9):1101-1112. doi: 10.1093/ecco-jcc/jjx056.


Background and aims: Inflammatory bowel disease [IBD] is characterised by a disruption of immune homeostasis, which is tightly regulated to protect against harmful pathogens yet not react to commensal antigens. Animal studies indicate that regulatory T cells [Treg] modulate the immune response to prevent IBD development. Lactoferrin [LF] is an endogenous anti-inflammatory pleiotropic protein secreted at high concentrations in colostrum and at mucosal sites. However, the effect of LF on specific T lymphocyte populations has not been studied. Here, we identify a novel mechanism by which a recombinant human LF, VEN-120, regulates T cell populations in health and disease.

Methods: Two murine models of intestinal inflammation, the dextran sodium sulphate colitis model and the TNFΔARE/+ model of ileitis, were used to study the anti-inflammatory and T cell modulating ability of VEN-120. Flow cytometry was used to evaluate T cell populations within the lamina propria and mesenteric lymph nodes, and to evaluate the effect of VEN-120 on CD4+ T cells in vitro.

Results: VEN-120 reduced inflammation in both models of IBD, accompanied by increased Tregs in the intestinal lamina propria. Treatment of CD4+ T cells in vitro resulted in an upregulation of Treg genes and skewing towards a Treg population. This in vitro T cell skewing translated to an increase of Treg homing to the intestinal lamina propria and associated lymph tissue in healthy mice.

Conclusions: These data provide a novel immunological mechanism by which VEN-120 modulates T cells to restrict inflammatory T cell-driven disease.

Keywords: VEN-120; colitis; lactoferrin; regulatory T cells.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Colitis / immunology*
  • Flow Cytometry
  • Humans
  • Ileitis / immunology*
  • Inflammatory Bowel Diseases / immunology*
  • Lactoferrin / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Phenotype*
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / immunology
  • T-Lymphocytes, Regulatory / immunology*


  • LTF protein, human
  • Recombinant Proteins
  • Lactoferrin