Interleukin-17A: A T-Cell Derived Growth Factor for Murine and Human Mesenchymal Stem Cells

¹ Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama
² Department of Pharmacology, Tulane University, New Orleans, Louisiana

^* To whom correspondence should be addressed. E-mail: poschwarz{at}yahoo.com.

	Abstract

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 (MSC) and induced the proliferation of mature stroma cells in bone marrow derived stroma cultures. rhIL-17A nearly doubled CFU-f frequency and almost tripled the surface area covered by stroma. In a murine transplant model, in vivo mIL-17A expression enhanced CFU-f by 2.5-fold. Enrichment of the graft with CD4+ T-cell resulted in 7.5-fold increase in CFU-f in normal C57BL/6, but only 3-fold 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.