Spatial Distribution of Mast Cells Regulates Asymmetrical Angiogenesis at the Ocular Surface

Cho, Wonkyung; Mittal, Sanjay; Elbasiony, Elsayed; Chauhan, Sunil

doi:10.1016/j.ajpath.2021.02.016

Cited by 10 publications

(7 citation statements)

References 47 publications

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“…Grafts were examined by slit lamp biomicroscopy once weekly for 8 weeks posttransplant (Figure 7A). As neovascularization is a common clinical parameter to monitor inflammatory corneal graft rejection and is strongly correlated with increased infiltration of immune cells to the graft site, 35,36 we quantified the degree of neovascularization (Figure 7B). Host mice treated with Mock‐MSCs exhibited a significant reduction in neovascularization compared to saline‐treated recipients, which was not observed in CD80‐silenced MSCs treated mice ( p = .004 and p = .003, respectively; Figure 7B).…”

Section: Resultsmentioning

confidence: 99%

Mesenchymal stem cells augment regulatory T cell function via CD80-mediated interactions and promote allograft survival

Mittal

Cho

Elbasiony

et al. 2022

American Journal of Transplantation

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Mesenchymal stem cells (MSCs) and regulatory T cells (Tregs) both have been shown to modulate the alloimmune response and promote transplant survival. Mounting evidence suggests that MSCs augment Treg function, but the mechanisms underlying this phenomenon have not been fully deciphered. Here, we identified that MSCs express substantial levels of CD80 and evaluated its immunoregulatory function using in vivo and in vitro experiments. Our in vitro culture assays demonstrated that MSCs induce expression of FoxP3 in Tregs in a contact‐dependent manner, and the blockade of CD80 abrogates this FoxP3 induction and Treg‐mediated suppression of T cell proliferation. Moreover, supplementation of soluble CD80 significantly upregulated FoxP3 expression. Using a well‐characterized murine model of corneal transplantation, we show that silencing CD80 in MSCs diminishes the capacity of MSCs to promote selective graft infiltration of Tregs, promote FoxP3 expression and upregulate suppressive function of Tregs. Consequently, MSCs, following CD80 knockdown, failed to promote corneal allograft survival.

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Section: Resultsmentioning

confidence: 99%

Mesenchymal stem cells augment regulatory T cell function via CD80-mediated interactions and promote allograft survival

Mittal

Cho

Elbasiony

et al. 2022

American Journal of Transplantation

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“…Sample sizes were estimated based on previous reports on corneal injury and inflammation. 11,16,17 3 | RESULTS…”

Section: Discussionmentioning

confidence: 99%

“…Quantification of images of corneal injury, CFS, scratch assay, as well as in vivo evaluations, was performed in a masked fashion. Sample sizes were estimated based on previous reports on corneal injury and inflammation 11,16,17 …”

Section: Methodsmentioning

confidence: 99%

Non‐immune and immune functions of interleukin‐36γ suppress epithelial repair at the ocular surface

et al. 2022

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Regulation of innate inflammation is critical for maintaining tissue homeostasis and barrier function, especially in those interfacing the external environments such as the skin and cornea. Expression of pro‐inflammatory cytokines by injured tissues has been shown to exacerbate the inflammatory cascade, causing tissue damage. Interleukin 36, a subfamily of the IL‐1 superfamily, consists of three pro‐inflammatory agonists—IL36α, IL36β, and IL36γ and an IL36 receptor antagonist (IL36Ra). The current investigation, for the first time, reports that IL36γ is the primary agonist expressed by the corneal epithelium, which is significantly upregulated following corneal injury. The function of IL36γ on non‐immune cells, in addition to innate inflammatory cells, in regulating tissue homeostasis has not been well investigated. Using a loss‐of‐function approach via neutralizing antibody treatment, our data demonstrate that blocking endogenously expressed IL36γ in epithelial cells promotes rapid re‐epithelialization in in vitro wound closure assay. Finally, by utilizing a naturally occurring antagonist IL36Ra in a well‐established murine model of ocular injury, our study demonstrates that inhibition of IL36γ accelerates epithelial regeneration and suppresses tissue inflammation. Given rapid wound healing is critical for re‐establishing normal tissue structure and function, our investigation on the function of IL36γ provides evidence for the development of novel IL36γ‐targeting strategies to promote tissue repair.

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“…Mast Cell Degranulation Assay Kit (Sigma–Aldrich) were used to quantify levels of tryptase 47 . The kit detects the chromophore p-nitroaniline (pNA) cleaved from the labeled substrate tosyl-gly-pro-lys-pNA.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2023

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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. We and others have previously shown that mast cells mediate tissue inflammation by recruiting other immune cells. However, despite their well-known characteristics of secreting various inflammatory mediators, whether mast cells contribute to the immune cell aggregation and activation, and acinar dystrophy of the aged lacrimal gland has not been investigated. Here, we demonstrate the role of mast cells in age-related lacrimal gland pathophysiology using mast cell-deficient (cKitw-sh) mice. Our data demonstrated a significant increase in mast cell frequencies and immune cell infiltration in the lacrimal gland of aged mice. Interestingly, mast cell deficiency resulted in a substantial reduction in inflammation and preservation of lacrimal gland structure, suggesting that mast cells mediate the aging process of the lacrimal gland.

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Spatial Distribution of Mast Cells Regulates Asymmetrical Angiogenesis at the Ocular Surface

Cited by 10 publications

References 47 publications

Mesenchymal stem cells augment regulatory T cell function via CD80-mediated interactions and promote allograft survival

Mesenchymal stem cells augment regulatory T cell function via CD80-mediated interactions and promote allograft survival

Non‐immune and immune functions of interleukin‐36γ suppress epithelial repair at the ocular surface

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

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