Mesenchymal stromal cells protect tissues from Th1 immune responses via IL‐11 secretion

Abstract

Mesenchymal 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.