Interleukin 17 (IL-17) Regulates the Recruitment of Early Stromal Progenitors into Colony Formation

Abstract 832

Interactions between T-cells and stromal cells of the microenvironment are important for stem cell growth and differentiation. IL-17 is a novel cytokine produced by a subset of regulatory T-cells (TCR+, CD4-, CD8) and targets stromal fibroblasts to produce cytokines (IL-6, IL-8, G-CSF) which regulate the proliferation of hematopoietic progenitor cells. In this study we examined IL-17 regulation of stromal progenitor cells, CFU-STRO, colony forming potential from human marrow. Our objectives were to determine whether IL-17:(a) recruited CFU-STRO into colony formation, and (b) preferentially targeted subpopulations of stromal progenitors with high proliferative potential, HPP. The stromal progenitor cell pool was defined by two major populations as 2-week colony forming units and 4-week colony forming units. Stromal progenitor subtypes were defined as pure fibroblast colony forming units, CFU-STROf, and as multipotential, CFU-STROmix, by giving rise to fibroblasts as well as other cell types including adipocytes. Colony formation was evaluated by plating efficiency (colony numbers/2.5×10⁵ MNC plated), and colony size (mm²). Colonies >30mm² were defined as high proliferative progenitors (HPP). Two doses of IL-17, 5.0 ng/ml, and 50.0 ng/ml caused a significant increase in both colony numbers and size when compared to control. CFU-STRO colony frequency increased by 20% and 65%, and the average colony size also increased by 25% and 61% with these respective doses. There was also a dose responsive growth of all stroma covering the surface area of each plate by 50% and 163%. Further, IL-17 increased CFU-STRO (HPP) type colony formation by 50% and 150% by preferentially targeting CFU-STROmix by 37% and 96% when compared to a 3% and 37% increase in CFU-STROf. We conclude that IL-17 enhances overall plating efficiency and proliferation of CFU-STRO and preferentially targets multipotential CFU-STROmix HPP. These data indicate that IL-17 is a novel cytokine that regulates the proliferation of the stromal/mesenchymal stem cell pool.