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

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.