Protective Role of ICOS and ICOS Ligand in Corneal Transplantation and in Maintenance of Immune Privilege

Kunishige, Tomoyuki; Taniguchi, Hiroko; Terada, Misao; Akiba, Hisaya; Yagita, Hideo; Ryo, Akihide; Hori, Junko

doi:10.1167/iovs.16-20644

Cited by 12 publications

(13 citation statements)

References 34 publications

(56 reference statements)

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“…To further elucidate the mechanism of immune privilege for corneal transplantation, further immunologic analysis will be necessary. The cornea constitutively expresses various immune-regulating molecules, such as B7-H1, 8 CD95L, 35,36 GITR-L, 5 galectin-9, 10 and ICOS-ICOS ligand 12 in distinct localization patterns within the tissue. The fact that the immune privileged status of the cornea can be abolished by dysfunction of just one of these molecules suggests that each molecule plays a nonredundant or cooperative role in maintenance of immune privilege.…”

Section: Discussionmentioning

confidence: 99%

“…6 Our group has reported some of the molecules that contribute to ACAID and the immune suppressive ocular microenvironment for establishment of immune privilege for corneal transplantation. B7-H1, 8 glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITR-L), 5,9 galectin-9, 10,11 and inducible costimulatory molecule (ICOS) and ICOS ligand 12,13 are involved in immune suppression in the cornea and are essential for immune privilege for corneal transplantation. The molecular mechanisms of immune privilege in the eye are not fully understood.…”

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confidence: 99%

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VISTA Is Crucial for Corneal Allograft Survival and Maintenance of Immune Privilege

Kunishige

Taniguchi

Ohno

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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Citation: Kunishige T, Taniguchi H, Ohno T, Azuma M, Hori J. VISTA is crucial for corneal allograft survival and maintenance of immune privilege. Invest Ophthalmol Vis Sci. 2019;60:4958-4965. https://doi.org/ 10.1167/iovs.19-27322 PURPOSE. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel immune checkpoint receptor and ligand for regulating T cell proliferation and cytokine production. The purpose of the present study was to determine the role of VISTA in the immune privilege of corneal allografts.METHODS. Expression of VISTA mRNA in mouse eyes was assessed with reverse-transcription PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of BALB/c wildtype recipients treated with anti-VISTA mAb, and graft survival was assessed. A separate set of BALB/c mice treated with anti-VISTA mAb or rat IgG received injection of C57BL/6 splenocytes into the anterior chamber, and induction of allospecific anterior chamberassociated immune deviation (ACAID) was assessed. CD4 þ and CD8 þ T cells in the spleen were assessed with flow cytometry. RESULTS.VISTA mRNA was constitutively expressed in the cornea, and the expression of VISTA was localized to CD11b þ cells on the corneal stroma. Survival of allografts treated with anti-VISTA mAb was less than that of the control. ACAID was induced less efficiently in BALB/c mice treated with VISTA mAb. The proportions of CD8 þ T cells and CD8 þ CD103 þ T cells (CD8 þ T regulatory cells) in the spleen of BALB/c mice treated with anti-VISTA mAb were significantly lower than those of the control.CONCLUSIONS. VISTA may play an essential role in the acceptance of corneal allografts via involvement with allospecific ACAID, which suppresses T cell infiltration into the cornea.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

VISTA Is Crucial for Corneal Allograft Survival and Maintenance of Immune Privilege

Kunishige

Taniguchi

Ohno

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…As shown in Table 1, various immunomodulatory factors are expressed in corneal endothelial cells and in the iris-ciliary body. We have revealed that inhibitory costimulatory signaling molecules such as programmed death ligand-1 (PD-L1, B7-H1) [28], inducible costimulatory molecule ligand (ICOSL, B7-H2, B7-related protein (B7RP)-1) [29], V-domain Ig suppressor of T cell activation (VISTA, PD-1H) [30], glucocorticoid-induced tumor necrosis factor (TNF) receptor family-related protein ligand (GITRL) [31], and galectin-9 [32], are constitutively expressed in the corneal tissue and involved in immune suppression in the cornea (Figure 1). These inhibitory costimulatory signal molecules play an important role in the regulation of antigen-specific T-cell-mediated immune responses.…”

Section: Immune Suppressive Microenvironment In the Anterior Segment mentioning

confidence: 99%

“…ICOS/ICOSL (B7-H2, B7RP-1) signals have been implicated in the differentiation and function of T cells. In the eye, ICOSL mRNA is constitutively expressed in the cornea, iris-ciliary body and retina [29]. Corneal allograft survival in ICOS −/− recipients and wild-type (WT) recipients treated with anti-ICOSL mAb was significantly shorter than in control recipients.…”

Section: Icos Ligand and Icosmentioning

confidence: 99%

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Immune Checkpoints Contribute Corneal Immune Privilege: Implications for Dry Eye Associated with Checkpoint Inhibitors

Hori

Kunishige

Nakano

2020

IJMS

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The eye is provided with immune protection against pathogens in a manner that greatly reduces the threat of inflammation-induced vision loss. Immune-mediated inflammation and allograft rejection are greatly reduced in the eye, a phenomenon called ‘immune privilege’. Corneal tissue has inherent immune privilege properties with underlying three mechanisms: (1) anatomical, cellular, and molecular barriers in the cornea; (2) an immunosuppressive microenvironment; and (3) tolerance related to regulatory T cells and anterior chamber-associated immune deviation. This review describes the molecular mechanisms of the immunosuppressive microenvironment and regulatory T cells in the cornea that have been elucidated from animal models of ocular inflammation, especially those involving corneal transplantation, it also provides an update on immune checkpoint molecules in corneal and systemic immune regulation, and its relevance for dry eye associated with checkpoint inhibitor therapy.

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Immune tolerance induced in the anterior chamber ameliorates corneal transplant rejection

Sun,

Wang,

Bian

et al. 2023

Clinical Immunology

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Protective Role of ICOS and ICOS Ligand in Corneal Transplantation and in Maintenance of Immune Privilege

Abstract: The expression of ICOSL in the cornea and the ICOS-mediated induction of Foxp3+ CD4+ regulatory T cells may contribute to successful corneal allograft survival.

Cited by 12 publications

References 34 publications

VISTA Is Crucial for Corneal Allograft Survival and Maintenance of Immune Privilege

VISTA Is Crucial for Corneal Allograft Survival and Maintenance of Immune Privilege

Immune Checkpoints Contribute Corneal Immune Privilege: Implications for Dry Eye Associated with Checkpoint Inhibitors

Immune tolerance induced in the anterior chamber ameliorates corneal transplant rejection

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