Abstract
Interleukin-17A (IL-17A) is a proinflammatory cytokine expressed in activated T-cells. It is required for microbial host defense and is a potent stimulator of granulopoiesis. In a dose-dependent fashion, IL-17A expanded human mesenchymal stem cells (MSCs) and induced the proliferation of mature stroma cells in bone marrow-derived stroma cultures. Recombinant human interleukin-17A (rhIL-17A) nearly doubled colony-forming unit-fibroblast (CFU-f) frequency and almost tripled the surface area covered by stroma. In a murine transplant model, in vivo murine (m)IL-17A expression enhanced CFU-f by 2.5-fold. Enrichment of the graft with CD4+ T-cell resulted in a 7.5-fold increase in CFU-f in normal C57BL/6, but only threefold in IL-17Ra-/- mice on day 14 post-transplant. In this transplant model, in vivo blockade of IL-17A in C57BL/6 mice resembled the phenotype of IL-17Ra-/- mice. Approximately half of the T-cell-mediated effect on MSC recovery following radiation-conditioned transplantation was attributed to the IL-17A/IL-17Ra pathway. Pluripotent MSCs have the potential of regenerating various tissues, and mature stroma cells are critical elements of the hematopoietic microenvironment (HME). The HME is pivotal for formation and maintenance of functional blood cells. As a newly identified stroma cell growth factor, IL-17A might have potential applications for novel treatment approaches involving MSCs, such as tissue graft engineering.
| Original language | English |
|---|---|
| Pages (from-to) | 1512-1518 |
| Number of pages | 7 |
| Journal | Stem Cells |
| Volume | 24 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2006 |
Fingerprint
Keywords
- Hematopoeitic microenvironment
- Interleukin-17
- Mesenchymal stem cells
- Stroma
- T-cells
ASJC Scopus subject areas
- Cell Biology
Cite this
Interleukin-17A : A T-cell-derived growth factor for murine and human mesenchymal stem cells. / Huang, Weitao; La Russa, Vincent; Alzoubi, Azam; Schwarzenberger, Paul.
In: Stem Cells, Vol. 24, No. 6, 01.06.2006, p. 1512-1518.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interleukin-17A
T2 - A T-cell-derived growth factor for murine and human mesenchymal stem cells
AU - Huang, Weitao
AU - La Russa, Vincent
AU - Alzoubi, Azam
AU - Schwarzenberger, Paul
PY - 2006/6/1
Y1 - 2006/6/1
N2 - Interleukin-17A (IL-17A) is a proinflammatory cytokine expressed in activated T-cells. It is required for microbial host defense and is a potent stimulator of granulopoiesis. In a dose-dependent fashion, IL-17A expanded human mesenchymal stem cells (MSCs) and induced the proliferation of mature stroma cells in bone marrow-derived stroma cultures. Recombinant human interleukin-17A (rhIL-17A) nearly doubled colony-forming unit-fibroblast (CFU-f) frequency and almost tripled the surface area covered by stroma. In a murine transplant model, in vivo murine (m)IL-17A expression enhanced CFU-f by 2.5-fold. Enrichment of the graft with CD4+ T-cell resulted in a 7.5-fold increase in CFU-f in normal C57BL/6, but only threefold in IL-17Ra-/- mice on day 14 post-transplant. In this transplant model, in vivo blockade of IL-17A in C57BL/6 mice resembled the phenotype of IL-17Ra-/- mice. Approximately half of the T-cell-mediated effect on MSC recovery following radiation-conditioned transplantation was attributed to the IL-17A/IL-17Ra pathway. Pluripotent MSCs have the potential of regenerating various tissues, and mature stroma cells are critical elements of the hematopoietic microenvironment (HME). The HME is pivotal for formation and maintenance of functional blood cells. As a newly identified stroma cell growth factor, IL-17A might have potential applications for novel treatment approaches involving MSCs, such as tissue graft engineering.
AB - Interleukin-17A (IL-17A) is a proinflammatory cytokine expressed in activated T-cells. It is required for microbial host defense and is a potent stimulator of granulopoiesis. In a dose-dependent fashion, IL-17A expanded human mesenchymal stem cells (MSCs) and induced the proliferation of mature stroma cells in bone marrow-derived stroma cultures. Recombinant human interleukin-17A (rhIL-17A) nearly doubled colony-forming unit-fibroblast (CFU-f) frequency and almost tripled the surface area covered by stroma. In a murine transplant model, in vivo murine (m)IL-17A expression enhanced CFU-f by 2.5-fold. Enrichment of the graft with CD4+ T-cell resulted in a 7.5-fold increase in CFU-f in normal C57BL/6, but only threefold in IL-17Ra-/- mice on day 14 post-transplant. In this transplant model, in vivo blockade of IL-17A in C57BL/6 mice resembled the phenotype of IL-17Ra-/- mice. Approximately half of the T-cell-mediated effect on MSC recovery following radiation-conditioned transplantation was attributed to the IL-17A/IL-17Ra pathway. Pluripotent MSCs have the potential of regenerating various tissues, and mature stroma cells are critical elements of the hematopoietic microenvironment (HME). The HME is pivotal for formation and maintenance of functional blood cells. As a newly identified stroma cell growth factor, IL-17A might have potential applications for novel treatment approaches involving MSCs, such as tissue graft engineering.
KW - Hematopoeitic microenvironment
KW - Interleukin-17
KW - Mesenchymal stem cells
KW - Stroma
KW - T-cells
UR - http://www.scopus.com/inward/record.url?scp=33747599826&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33747599826&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2005-0156
DO - 10.1634/stemcells.2005-0156
M3 - Article
VL - 24
SP - 1512
EP - 1518
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 6
ER -