Glucocorticoids induce corneal allograft tolerance through expansion of monocytic myeloid-derived suppressor cells

Lee, Hyun Ju; Park, Se Yeon; Jeong, Hyun Jeong; Kim, Hyeon Ji; Kim, Mee Kum; Oh, Joo Youn

doi:10.1111/ajt.15026

Cited by 16 publications

(13 citation statements)

References 22 publications

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“…One is that RAPA nano-micelle inhibited corneal allograft rejection through regulating MDSC recruitment. Several studies indicated that RAPA could prolong cardiac-allograft survival and protect against murine immunological hepatic injury by promoting CD11b + Gr-1 int cells recruitment ( 28 , 41 ). Likewise, Choi et al reported that CD11b + Gr-1 int cells improved corneal allograft survival ( 27 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

Rapamycin Nano-Micelle Ophthalmic Solution Reduces Corneal Allograft Rejection by Potentiating Myeloid-Derived Suppressor Cells' Function

Wei

Wang

et al. 2018

Front. Immunol.

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Allograft rejection is the major cause of corneal allograft failure. Rapamycin (RAPA) has been reported as an effective and novel immunosuppressive agent for patients undergoing corneal transplantation. However, its high water insolubility and low bioavailability have strongly constrained its clinical application. In this study, we successfully developed a RAPA nano-micelle ophthalmic solution and found that corneal allograft survival in recipients treated with RAPA nano-micelle ophthalmic solution was significantly prolonged for more than 2 months, with less inflammatory infiltration, decreased production of pro-inflammatory factors, and elevated recruitment of myeloid-derived suppressor cells (MDSCs). MDSCs from mice treated with RAPA nano-micelle ophthalmic solution could significantly inhibit the proliferation of CD4+T cells through increased expressions of inducible nitric oxidase (iNOS) and arginase-1 (Arg-1). The activity blockade of Arg-1 and iNOS pharmacologically reversed their immunosuppressive ability. Moreover, the effects of RAPA were antagonized by the administration of anti-Gr-1 antibody or by inhibiting the activity of iNOS pharmacologically. In addition, RAPA nano-micelle also effectively alleviated allograft rejection in high-risk rabbit penetrating keratoplasty (PKP) models with corneal vascularization. Collectively, our results demonstrate that RAPA nano-micelle ophthalmic solution could improve the immunosuppressive activity of MDSCs through elevated expression of Arg-1 and iNOS, which highlights the possible therapeutic applications of RAPA against corneal allograft rejection.

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Section: Discussionmentioning

confidence: 99%

Rapamycin Nano-Micelle Ophthalmic Solution Reduces Corneal Allograft Rejection by Potentiating Myeloid-Derived Suppressor Cells' Function

Wei

Wang

et al. 2018

Front. Immunol.

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“…For example, it has been shown that the activity of MDSCs was impaired in mice and humans with systemic lupus erythematosus, inflammatory bowel disease, collagen-induced arthritis, and type 1 diabetes mellitus (3)(4)(5)(6). In addition, adoptive transfer of MDSCs has been reported to inhibit the progression of autoimmune arthritis and uveoretinitis (5,7,8), delay the onset of diabetes (9,10), and prolong the survival of corneal and skin allotransplants (11,12). These findings support the notion that MDSCs play a role in maintaining immune homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stromal cells induce distinct myeloid-derived suppressor cells in inflammation

Lee¹,

Ko²,

Kim³

et al. 2020

JCI Insight

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“…FACS-sorted CD11b + Ly6C + cells from bone marrow of dex-treated mice inhibited in vitro CD4+ T cells proliferation and prolonged the survival of corneal allografts when transferred into dex-untreated recipients. Depletion of MHC class II − CD11b + Ly6C + monocytes abrogated the protective effect of dex on corneal allografts suggesting that these cells were required for mediating the induction of tolerance by glucocorticoids (49). Similar results were obtained in corneal allograft recipient mice treated with a rapamycin nano-micelle (RNM) ophthalmic solution.…”

Section: Mdsc In Organ Transplantationmentioning

confidence: 99%

Tolerogenic Role of Myeloid Suppressor Cells in Organ Transplantation

et al. 2019

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Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells of myeloid origin with a specific immune inhibitory function that negatively regulates the adaptive immune response. Since MDSC participate in the promotion of tolerance in the context of organ transplantation, therapeutic strategies that regulate the induction and development of MDSC have been the center of scientist attention. Here we review literature regarding induction of MDSC with demonstrated suppressive function among different types of allografts and their mechanism of action. While manipulation of MDSC represents a potential therapeutic approach for the promotion of donor specific tolerance in solid organ transplantation, further characterization of their specific phenotype, which distinguishes MDSC from non-suppressive myeloid cells, and detailed evaluation of the inhibitory mechanism that determines their suppressive function, is necessary for the realistic application of MDSC as biomarkers in health and disease and their potential use as immune cell therapy in organ transplantation.

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Glucocorticoids induce corneal allograft tolerance through expansion of monocytic myeloid-derived suppressor cells

Cited by 16 publications

References 22 publications

Rapamycin Nano-Micelle Ophthalmic Solution Reduces Corneal Allograft Rejection by Potentiating Myeloid-Derived Suppressor Cells' Function

Rapamycin Nano-Micelle Ophthalmic Solution Reduces Corneal Allograft Rejection by Potentiating Myeloid-Derived Suppressor Cells' Function

Mesenchymal stromal cells induce distinct myeloid-derived suppressor cells in inflammation

Tolerogenic Role of Myeloid Suppressor Cells in Organ Transplantation

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