Affiliation:
1. Schepens Eye Research Institute of Mass Eye and Ear Harvard Medical School Boston Massachusetts USA
Abstract
AbstractMesenchymal stromal cells (MSCs) have been shown to modulate the function of various subsets of T cells such as naïve CD4+ T cells and IFNγ+CD4+ Th1 cells; however, mechanisms underlying this regulation have not been fully deciphered. Our in vitro culture assays demonstrate that MSCs suppress the activation and function of CD4+ T cells by secreting interleukin 11, and neutralization of IL11 abrogates MSC‐mediated suppression of CD4+ T cell function. Moreover, delayed‐type, exogenous supplementation of IL11 significantly suppressed IFNγ+ expression by Th1 cells. Th1 and CD8+ cells play central roles in T cell‐mediated tissue damage. Using a murine model of hypersensitivity response to study T cell‐mediated tissue damage, we show that silencing IL11 in MSCs significantly abates the capacity of MSCs to suppress the generation of IFNγ‐secreting CD4+ and CD8+ cells, failing to prevent T cell‐mediated tissue inflammation and tissue damage.