Myeloid‐derived suppressor cells (MDSC) are one of the major negative regulators of immune responses during many pathological conditions such as cancer and transplantation. Emerging evidence indicates that MDSC also contribute to tumor progression through their pro‐angiogenic activity in addition to immunosuppressive function. However, virtually nothing is known about the role of MDSC in the regulation of neovascularization after transplantation. Here we showed that antibody‐mediated depletion of MDSC in mice led to robust growth of blood and lymphatic neovessels and rapid allograft rejection after corneal penetrating keratoplasty. In contrast, adoptive transfer of ex vivo generated MDSC from cytokine‐treated bone marrow cells (evMDSC) suppressed neovascularization and prolonged corneal allograft survival in an inducible nitric oxide synthase (iNOS)‐dependent manner. Mechanistically, compared to naïve MDSC control, evMDSC have increased expression of an anti‐angiogenic factor thrombospondin 1 (Tsp‐1) and decreased expression of two critical pro‐angiogenic factors, vascular endothelial growth factor A (VEGF‐A), and VEGF‐C. These findings demonstrate MDSC as a critical anti‐angiogenic regulator during transplantation. Our study also indicates that evMDSC are a valuable candidate agent for development of novel cell therapy to improve allograft survival after transplantation.
Background Autoimmune blistering skin diseases (AIBD) are a group of rare chronic autoimmune diseases which are associated with ocular surface diseases especially dry eye disease. This study is designed to investigate the relationship between ocular surface disorders and quality of life among patients with autoimmune blistering skin diseases. Methods Twenty-four AIBD patients (18 pemphigus and 7 pemphigoid) and twenty-five non-AIBD controls were included. Ocular surface disease index (OSDI), ocular surface evaluation, including slit-lamp examination, Schirmer I test, tear break-up time, corneal fluorescein staining, lid-parallel conjunctival folds, meibomian gland evaluation, presence of symblepharon and corneal opacity were assessed. Life quality was evaluated by multiple questionnaires, including Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Ocular surface tests and quality of life were compared between AIBD patients and non-AIBD controls. In the AIBD patients, the associations between ocular surface parameters and quality of life were also evaluated. Results 92% of AIBD patients and 87.5% of age- and sex-matched non-AIBD controls were diagnosed with dry eye in this study. Compared with non-AIBD controls, AIBD patients reported lower SF-36 scores (P < 0.05) and severer OSDI, Schirmer I test, tear break-up time, corneal fluorescein staining, presence of symblepharon and corneal opacity measures (P < 0.05). OSDI, Schirmer I test were correlated with SF-36 composite scores or scores on the SF-36 subscales. Conclusions AIBD patients experience reduced quality of life and more severe ocular surface disorders including dry eye, symblepharon and corneal opacity. Early treatments of dry eye and collaborations among multidisciplinary physicians are necessary in patients with AIBD.
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