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

Kunishige, Tomoyuki; Taniguchi, Hiroko; Ohno, Tomohiro; Azuma, Miyuki; Hori, Junko

doi:10.1167/iovs.19-27322

Cited by 11 publications

(12 citation statements)

References 36 publications

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“…We have expanded upon these data and showed that selective targeting of donor alloreactive T cells is sufficient for the anti‐VISTA prophylactic effect in GVHD . Of relevance, a recent study found that VISTA was expressed by myeloid cells of the corneal stroma and that genetic deficiency or blockade of VISTA significantly reduced corneal allograft survival . We have observed similar results where VISTA‐deficiency or blockade also markedly reduced skin graft tolerance and survival and superseded the immunosuppressive effects of CD40L blockade (ElTanbouly and LeMercier, unpublished observations).…”

Section: Vista‐deficiency Enhances Immunitymentioning

confidence: 68%

VISTA: Coming of age as a multi-lineage immune checkpoint

ElTanbouly

Schaafsma

Noelle

et al. 2020

Clinical and Experimental Immunology

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The immune response is governed by a highly complex set of interactions among cells and mediators. T cells may be rendered dysfunctional by the presence of high levels of antigen in the absence of co-stimulation while myeloid cells may be programmed towards an immunosuppressive state that promotes cancer growth and metastasis while deterring tumor immunity. In addition, inhibitory programs driven by immune checkpoint regulators dampen anti-tumor immunity. The ideal cancer immunotherapy treatment will improve both cross-priming in the tumor microenvironment and relieve suppression by the inhibitory checkpoints. Recently, blockade of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) has elicited impressive results, but not in all patients, so additional targets are under investigation. V-set immunoglobulin domain suppressor of T cell activation (VISTA) is a novel immunoregulatory receptor that is broadly expressed on cells of the myeloid and lymphoid lineages, and is frequently implicated as a poor prognostic indicator in multiple cancers. Importantly, antibody targeting of VISTA uniquely engages both innate and adaptive immunity. This, combined with the expression of VISTA and its non-redundant activities compared to other immune checkpoint regulators, qualifies VISTA to be a promising target for improving cancer immunotherapy.

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Section: Vista‐deficiency Enhances Immunitymentioning

confidence: 68%

VISTA: Coming of age as a multi-lineage immune checkpoint

ElTanbouly

Schaafsma

Noelle

et al. 2020

Clinical and Experimental Immunology

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“…In a model of experimental asthma, VISTA deficiency and blockade exacerbated Th2 responses and type II immunity ( 11 , 22 ), whereas an anti-VISTA agonistic antibody reduces disease severity and suppressed lung inflammation ( 22 ). There are reported roles of VISTA deficiency in several other inflammatory diseases including psoriasis, transplant rejection, acute hepatitis, and indicate a potential value of VISTA agonists in these immunopathologies ( 12 , 23 , 24 ).…”

Section: Targeting Vista With Agonists Suppresses Multiple Inflammatomentioning

confidence: 99%

VISTA: A Target to Manage the Innate Cytokine Storm

et al. 2021

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In recent years, the success of immunotherapy targeting immunoregulatory receptors (immune checkpoints) in cancer have generated enthusiastic support to target these receptors in a wide range of other immune related diseases. While the overwhelming focus has been on blockade of these inhibitory pathways to augment immunity, agonistic triggering via these receptors offers the promise of dampening pathogenic inflammatory responses. V-domain Ig suppressor of T cell activation (VISTA) has emerged as an immunoregulatory receptor with constitutive expression on both the T cell and myeloid compartments, and whose agonistic targeting has proven a unique avenue relative to other checkpoint pathways to suppress pathologies mediated by the innate arm of the immune system. VISTA agonistic targeting profoundly changes the phenotype of human monocytes towards an anti-inflammatory cell state, as highlighted by striking suppression of the canonical markers CD14 and Fcγr3a (CD16), and the almost complete suppression of both the interferon I (IFN-I) and antigen presentation pathways. The insights from these very recent studies highlight the impact of VISTA agonistic targeting of myeloid cells, and its potential therapeutic implications in the settings of hyperinflammatory responses such as cytokine storms, driven by dysregulated immune responses to viral infections (with a focus on COVID-19) and autoimmune diseases. Collectively, these findings suggest that the VISTA pathway plays a conserved, non-redundant role in myeloid cell function.

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“…In the eye, VISTA mRNA is constitutively expressed in the cornea, and the expression of VISTA is localized to CD11b + cells on the corneal stroma [30]. The survival of corneal allograft in the recipients treated with anti-VISTA mAb was less than that of the control.…”

Section: Vista(pd-1h)mentioning

confidence: 99%

“…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%

“…The proportions of CD8 + T cells and CD8 + CD103 + T cells (CD8 + T regulatory cells) in the spleen of BALB/c mice treated with anti-VISTA mAb were significantly lower than those of the control. Thus, VISTA plays an essential role in the induction of ACAID via CD8 + CD103 + T regulatory cells which suppresses T cell infiltration into the cornea [30] (Figure 3).…”

Section: Vista(pd-1h)mentioning

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

Self Cite

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

Cited by 11 publications

References 36 publications

VISTA: Coming of age as a multi-lineage immune checkpoint

VISTA: Coming of age as a multi-lineage immune checkpoint

VISTA: A Target to Manage the Innate Cytokine Storm

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

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