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Joy Sarkar, Eunjae Kim, Shweta Chaudhary, Yong Soo Byun, Sapna Tibrewal, Yair Ivanir, Rama Wahood, Neil Mohindra, Kaele Leonard, Sandeep Jain; Neuroregenerative and Immunosuppressive actions of Myeloid-derived Suppressor Cells (MDSCs) in the Cornea. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4721.
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To investigate whether myeloid-derived suppressor cells (MDSCs) in the cornea have neuroregenerative and immunosuppressive action
Corneal inflammation was induced in Thy1-YFP neurofluorescent homozygous adult mice (8-10week old) with 0.1% Benzalkonium chloride (BAK) eye drops for 1 week. Serial in vivo imaging was performed using a fluorescent stereomicroscope to visualize corneal nerves and infiltrating fluorescent inflammatory cells. YFP+MDSCs obtained from mouse bone marrows and corneas were used to evaluate their neuroregenerative potential and immunosuppressive action. Increased neurite length in compartmental and transwell culture of trigeminal ganglion (TG) neurites in the presence YFP+MDSCs, as well as upregulation of specific neurotrophins and regeneration-associated genes were quantified using quantitative PCR and ELISA to evaluate neurotrophic potential. Allogeneic Mixed Lymphocyte (MLR) was performed to evaluate the immunosuppressive actions of YFP+MDSCs
Following BAK-induced corneal inflammation, YFP+MDSCs infiltrated the cornea and demonstrated immunosuppressive effects as evidenced by their suppression of T-cell proliferation in allogeneic MLR. Furthermore, these cells showed an up-regulation of immunosuppressive markers, namely IL-10, Arginase-1, and 2 mRNA levels. In compartmental culture, TG neurites demonstrated increased growth in the presence of YFP+MDSCs as well as upregulation of neurotrophins and secreted NGF in conditioned medium.
YFP+MDSCs in the cornea exhibit immunosuppressive and neurotrophic actions in the cornea thus linking the myeloid/immune and neuronal systems. Our findings point to cell-based strategies for influencing neuronal disease or injury.
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