TIMP-2 Promotes Wound Healing by Suppressing Matrix Metalloproteinases and Inflammatory Cytokines in Corneal Epithelial Cells.

Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix (ECM) remodeling for maintaining homeostasis and promoting cell migration and proliferation. Pathological conditions can alter TIMP homeostasis and aggravate disease progression. The roles of TIMPs have been studied in tissue-related disorders; however, their contributions to tissue repair during corneal injury are undefined.

Hepatocyte growth factor upregulates MMP1 and MMP10 expression and resolves corneal fibrosis.

Different therapeutic modalities, including steroids, have been used to treat corneal scarring. However, the ability of steroids to reduce corneal scarring is limited and associated with numerous side effects. Our previous studies have demonstrated that topical hepatocyte growth factor (HGF) after corneal injury suppresses the development of stromal scars.

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 IFNγCD4 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.

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.

Mesenchymal Stromal Cells Suppress T-Cell-Mediated Delayed-Type Hypersensitivity via ALCAM-CD6 Interaction.

Mounting evidence suggests mesenchymal stromal cells (MSCs) suppress CD4+ T-cell activation, but whether MSCs directly regulate activation and expansion of allogeneic T cells has not been fully deciphered. Here, we identified that both human and murine MSCs constitutively express ALCAM, a cognate ligand for CD6 receptors on T cells, and investigated its immunomodulatory function using in vivo and in vitro experiments. Our controlled coculture assays demonstrated that ALCAM-CD6 pathway is critical for MSCs to exert its suppressive function on early CD4+CD25- T-cell activation.

Increased activity of lacrimal gland mast cells are associated with corneal epitheliopathy in aged mice.

The lacrimal gland undergoes significant structural and functional deterioration with aging. Marked with increased inflammation and fibrosis, the aged lacrimal gland is unable to perform its protective function. As a result, the ocular surface becomes highly susceptible to various ocular surface pathologies, including corneal epitheliopathy.

IL-36γ Augments Ocular Angiogenesis by Promoting the Vascular Endothelial Growth Factor-Vascular Endothelial Growth Factor Receptor Axis.

Prevention of inflammatory angiogenesis is critical for suppressing chronic inflammation and inhibiting inflammatory tissue damage. Angiogenesis is particularly detrimental to the cornea because pathologic growth of new blood vessels can lead to marked vision impairment and even loss of vision. The expression of proinflammatory cytokines by injured tissues exacerbates the inflammatory cascade, including angiogenesis.