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.

Interleukin-11 Suppresses Ocular Surface Inflammation and Accelerates Wound Healing.

Purpose: Regulation of inflammation is critical for achieving favorable outcomes in wound healing. In this study, we determine the functional role and mechanism of action of IL-11, an immunomodulatory cytokine, in regulating inflammatory response at the ocular surface. Methods: Corneal injury was induced by mechanical removal of the epithelium and anterior stroma using an AlgerBrush II. Transcript and protein levels of IL-11 in injured cornea were quantified using real-time PCR and ELISA analysis. Corneal inflammation was assessed by measuring frequencies of total CD45+ inflammatory cells, CD11b+Ly6G+ polymorphonuclear cells (neutrophils), and CD11b+Ly6G- mononuclear cells (macrophages, monocytes) at the ocular surface using flow cytometry. To assess the effect of IL-11 on innate immune cell function, cell activation marker and inflammatory cytokines including major histocompatibility complex (MHC) class II, myeloperoxidase (MPO), TNFα, and inducible nitric oxide synthase (iNOS) were measured following recombinant IL-11 treatment (1 µg/mL). Injured corneas were topically treated with IL-11 (1 µg/mL), and wound healing was evaluated using corneal fluorescein staining. Results: Corneal injury resulted in increased levels of IL-11 in the cornea, particularly in the stroma. Neutrophils and CD11b+ mononuclear cells (macrophages, monocytes) substantially expressed IL-11 receptor. Interestingly, IL-11 significantly downregulated the activation of immune cells, as evidenced by the lower expression of MHC II and TNFα by CD11b+ mononuclear cells and lower levels of MPO by neutrophils. Topical administration of IL-11 to injured corneas led to faster wound healing and better retention of tissue architecture. Conclusions: Our findings demonstrate IL-11 is a key modulator of ocular surface inflammation and provide novel evidence of IL-11 as a potential therapeutic to control inflammatory damage and accelerate wound repair following injury.