LACTOFERRIN COMPOSITIONS AND METHODS FOR MODULATION OF T CELL SUBTYPES AND TREATMENT OF AUTOIMMUNE DISEASES
Methods of inducing a regulatory T cell (Treg) phenotype and skewing naïve T cells toward a pro-regulatory phenotype are disclosed.
1 . A method for inducing a regulatory T cell (Treg) phenotype, said method comprising contacting an initial population of T cells with lactoferrin, wherein said T cells exhibit a Treg phenotype after said contacting.
2 . The method of claim 1 , said method comprising activating T cells in the presence of said lactoferrin.
3 . The method of claim 1 , said method comprising stimulating T cells in the presence of said lactoferrin.
4 . The method of claim 1 , said method comprising culturing said T cells in the presence of said lactoferrin.
5 . The method of claim 1 , wherein said initial population of T cells comprises CD4+ and/or CD8+ T cells.
6 . The method of claim 1 , wherein said initial population of T cells is induced towards a Treg phenotype and away from a proinflammatory Th1/17 phenotype.
7 . The method of claim 1 , wherein said Treg phenotype comprises FoxP3 expression.
8 . The method of claim 1 , wherein said Treg phenotype is increased in said population of cells, and wherein any conversion of said T cells into Th1 cells is decreased as compared to a control.
9 . The method of claim 1 , wherein a Th1/Th17 T cell phenotype is inhibited in said population of T cells.
10 . The method of claim 1 , wherein said method comprises upregulating genes (Fosl1, Foxp3, Ikzf2, Irf1, Irf4, and/or Tgif) involved in Treg generation, and concomitantly downregulating genes (Il-17a, Il17re, and/or Rora) involved in regulating Th17 phenotype.
11 . The method of claim 1 , further comprising expanding said population of T cells to increase said Treg cells.
12 . The method of claim 1 , wherein said lactoferrin is native lactoferrin isolated and purified from a mammal or mammalian secretion.
13 . The method of claim 1 , wherein said lactoferrin is mammalian lactoferrin recombinantly expressed in a host system.
14 . The method of claim 13 , wherein said host system is a plant, microorganism, yeast, fungi, insect system, or animal cell system.
15 . The method of claim 1 , wherein said contacting is carried out in an in vitro culture system.
16 . The method of claim 1 , wherein said population of T cells has an increase in Treg numbers.
17 . The method of claim 1 , wherein said Tregs express increased levels of IL-10.