Defining a Novel Therapeutic Application of Lactoferrin for Intestinal Inflammation
Abstract
Anti-inflammatory Foxp3+CD4+ Tregs are critical for the maintenance of immune homeostasis both systemically and in the gastrointestinal tract. Tregs quell an overactive immune response in the intestinal mucosa. The microbiome plays a critical role in this homeostasis, in part through activation of Tregs. Disruption of immune homeostasis is a key factor in development of intestinal inflammation. Many current therapies for inflammatory conditions inhibit the entire immune response without sparing Tregs, thus inhibiting the body's anti-inflammatory response. Selected activation of Tregs, rather than whole-sale suppression of the immune system, could provide a more efficacious and better-tolerated means of restoring immune homeostasis; furthermore, this approach may lend itself to prophylactic measures designed to protect individuals at risk for intestinal inflammation. Our preclinical studies demonstrated that the human iron-binding glycoprotein, LF, ameliorates inflammation and specifically activates the Treg population. The molecular mechanisms through which LF exerts its anti-inflammatory effects and promotes immune homeostasis are not well understood but are likely to occur through multiple pathways. Our ongoing studies effectively demonstrate the therapeutic potential of orally delivered LF in distinct murine models of IBD. Yet, the best therapeutic strategy and formulation for LF delivery (e.g., iron free or iron saturated) for enteric infection vs chronic inflammation have not been examined. Addressing these questions is essential for development of LF as a new treatment option for intestinal inflammation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1190414
Entities
People
- Daniel N. Frank
- Edwin F. De Zoeten
Organizations
- University of Colorado Boulder