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

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.

Author information

1
Ventria Biosciences, Fort Collins, CO, USA.
2
Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
3
Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, USA.

Abstract

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

PMID:
28472424
PMCID:
PMC5881664
DOI:
10.1093/ecco-jcc/jjx056
[Indexed for MEDLINE]
Free PMC Article

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