Interleukin 17 (IL-17) regulates the recruitment of early stromal progenitors into colony formation

A. Alzoebie, P. Schwarzenberger, A. Miller, J. K. Kolls, C. D. Scher, R. P. Wamer, V. F. La Russa

Research output: Contribution to journalArticle

Abstract

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/ 2.5xl05 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.

Original languageEnglish
JournalExperimental Hematology
Volume26
Issue number8
StatePublished - Dec 1 1998

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Interleukin-17
Cytokines
Cellular Microenvironment
Regulatory T-Lymphocytes
Stromal Cells
Growth
Mesenchymal Stromal Cells
Cell Differentiation
Stem Cells
T-Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Alzoebie, A., Schwarzenberger, P., Miller, A., Kolls, J. K., Scher, C. D., Wamer, R. P., & La Russa, V. F. (1998). Interleukin 17 (IL-17) regulates the recruitment of early stromal progenitors into colony formation. Experimental Hematology, 26(8).

Interleukin 17 (IL-17) regulates the recruitment of early stromal progenitors into colony formation. / Alzoebie, A.; Schwarzenberger, P.; Miller, A.; Kolls, J. K.; Scher, C. D.; Wamer, R. P.; La Russa, V. F.

In: Experimental Hematology, Vol. 26, No. 8, 01.12.1998.

Research output: Contribution to journalArticle

Alzoebie, A, Schwarzenberger, P, Miller, A, Kolls, JK, Scher, CD, Wamer, RP & La Russa, VF 1998, 'Interleukin 17 (IL-17) regulates the recruitment of early stromal progenitors into colony formation', Experimental Hematology, vol. 26, no. 8.
Alzoebie A, Schwarzenberger P, Miller A, Kolls JK, Scher CD, Wamer RP et al. Interleukin 17 (IL-17) regulates the recruitment of early stromal progenitors into colony formation. Experimental Hematology. 1998 Dec 1;26(8).
Alzoebie, A. ; Schwarzenberger, P. ; Miller, A. ; Kolls, J. K. ; Scher, C. D. ; Wamer, R. P. ; La Russa, V. F. / Interleukin 17 (IL-17) regulates the recruitment of early stromal progenitors into colony formation. In: Experimental Hematology. 1998 ; Vol. 26, No. 8.
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abstract = "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/ 2.5xl05 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.",
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