A Novel Pro-Angiogenic Function for Interferon-γ–Secreting Natural Killer Cells

Lee, Hyunsoo; Schlereth, Simona L.; Park, Eun Young; Emami-Naeini, Parisa; Chauhan, Sunil; Dana, Reza

doi:10.1167/iovs.14-14093

Cited by 37 publications

(34 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We show for the first time that alloreactive host T cells promote angiogenesis after transplantation, largely through expression of VEGF-A. Accordingly, we propose that the angiogenic process following corneal transplantation develops in 2 phases: an early phase related to the postoperative healing process mediated by innate immune cells, as described elsewhere, 56–58 and a late phase mediated by alloreactive T cells responsible for graft rejection.…”

Section: Discussionsupporting

confidence: 64%

Proangiogenic Function of T Cells in Corneal Transplantation

Zazzo

Tahvildari²,

Subbarayal³

et al. 2017

Transplantation

Self Cite

View full text Add to dashboard Cite

Background Corneal neovascularization increases the risk of T cell mediated allograft rejection. Here, we investigate whether T cells promote angiogenesis in transplantation. Methods Conventional effector T cells were collected from draining lymph nodes (DLNs) of allogeneic or syngeneic corneal transplanted BALB/c mice. T cells were either cocultured with vascular endothelial cells (VECs) to assess VEC proliferation or used in a Mixed Lymphocyte Reaction assay. mRNA expression of vascular endothelial growth factor (VEGF)-A, -C, and VEGF receptor 2 (VEGF-R2) in VECs was assessed by real-time PCR. VEGF-A protein expression was determined by ELISA. Flow cytometry was used to analyze VEGF-R2 expression in corneal CD31+ cells, and VEGF-A and IFNγ expression in corneal CD4+ T cells. Results Allogeneic T cells from high-risk (HR) grafted mice induced more VEC proliferation than those from syngeneic transplant recipients (p=0.03). VEGF-A mRNA and protein expression were higher in T cells from DLNs (p=0.03 and p=0.04, respectively) and cornea (protein; p=0.04) of HR compared to low-risk (LR) grafted hosts. VEGF-A, VEGF-C and VEGF-R2 mRNA expression were increased in VECs when cocultured with T cells from HR transplants compared to LR transplants and naïve mice. In addition, IFNγ blockade in T cell/VEC coculture increased VEC proliferation and VEGF-A protein expression, whereas blocking VEGF-A significantly reduced VEC proliferation (p=0.04). Conclusions Allogeneic T cells from corneal transplant hosts promote VEC proliferation, probably via VEGF-A signaling, while IFNγ shows an antiangiogenic effect. Our data suggest that T cells are critical mediators of angiogenesis in transplantation.

show abstract

Section: Discussionsupporting

confidence: 64%

Proangiogenic Function of T Cells in Corneal Transplantation

Zazzo

Tahvildari²,

Subbarayal³

et al. 2017

Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, we showed that when the epithelium is challenged with flagellin, CXCL10 was expressed in the basal epithelial cells and a group of CXCX3 positive cells were seen lining as a single layer underneath the epithelial layer in the stroma; these cells were shown to be natural killer (NK) cells [32]. NK cells have been shown to possess pro-angiogenic property in non-small cell lung cancer [48], to remodel maternal vasculature in early pregnancy [49], and to induce angio-genesis by promoting enhanced VEGF expression by macrophages in the cornea micropocket assays and the laser-induced choroidal neovascularization mouse models (C57BL/6) [50]. It is, however, unclear if the pro-angiogenic effects are related to inflammation mediated by NK cells which are known to be a major source of interferon-γ [50].…”

Section: Discussionmentioning

confidence: 99%

“…NK cells have been shown to possess pro-angiogenic property in non-small cell lung cancer [48], to remodel maternal vasculature in early pregnancy [49], and to induce angio-genesis by promoting enhanced VEGF expression by macrophages in the cornea micropocket assays and the laser-induced choroidal neovascularization mouse models (C57BL/6) [50]. It is, however, unclear if the pro-angiogenic effects are related to inflammation mediated by NK cells which are known to be a major source of interferon-γ [50]. Since our data indicates that epithelial expression of CXCL10 is anti-angiogenic, it is likely that CXCL10, in addition to being a chemokine, may directly act on both hem-and lymph-endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13

Gao

Liu

et al. 2017

Angiogenesis

View full text Add to dashboard Cite

Though not present in the normal adult cornea, both hem- and lymph-angiogenesis can be induced in this tissue after an inflammatory, infectious, or traumatic insult. We previously showed that the chemokine CXCL10 plays a key role in eradicating invading Candida (C.) albicans in C57BL6 mouse corneas. However, even after the clearance of pathogens, infection-induced inflammation and angiogenesis continue to progress in the cornea. The aim of this study is define the role of CXCL10 as a major angiostatic factor in modulating cornea angiogenesis in B6 mouse corneas under pathogenic conditions. We showed that epithelial expression of CXCL10, driven by AAV9 vector, suppressed both infection- and inflammation-induced hem and lymph angiogenesis, whereas the neutralization of CXCL10 as well as its receptor CXCR3 greatly promoted these processes. The inhibitory effect of CXCL10 was unrelated to its antimicrobial activity, but through the suppression of the expression of many angiogenic factors, including VEGFa and c, and MMP-13 in vivo. Inhibition of MMP13 but not TIMPs, attenuated suture-induced neovascularization but had no effects on CXCL10 expression. Strikingly, topical application of CXCL10 post-C. albicans infection effectively blocked both hem- and lymph-angiogenesis and preserved the integrity of sensory nerves in the cornea. Taken together, CXCL10 has strong inhibitory effects on neovascularization, whereas MMP13 is required for neovascularization in C. albicans-infected corneas and the local application of CXCL10 or MMP13 inhibitors, alone or as adjuvant therapy, may target hem- and lymph-angiogenesis in the inflamed corneas.

show abstract

“…Angiogenesis and blood vessel remodeling are vital steps in metastatic processes, and several research studies reported that IFN‐γ‐secreting NK cells function in favor of them . Similarly, melanoma cells aggressiveness can be increased via NK cells and also it might favor these cells to shift from proliferative to invasive forms through inducing stemless upregulation or typical markers of epithelial‐mesenchymal transition (EMT).…”

Section: The Factors and Mechanisms By Which Ilcs Enhance Tumor Progrmentioning

confidence: 99%

Progression or suppression: Two sides of the innate lymphoid cells in cancer

Hosseini

Sharafkandi

Seyfizadeh

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

Innate lymphoid cells (ILCs) as key players in innate immunity have been shown to be significantly associated with inflammation, lymphoid neogenesis, tissue remodeling, mucosal immunity and lately have been considered a remarkable nominee for either tumor‐promoting or tumor‐inhibiting functions. This dual role of ILCs, which is driven by intrinsic and extrinsic factors like plasticity of ILCs and the tumor microenvironment, respectively, has aroused interest in ILCs subsets in past decade. So far, numerous studies in the cancer field have revealed ILCs to be key players in the initiation, progression and inhibition of tumors, therefore providing valuable insights into therapeutic approaches to utilize the immune system against cancer. Herein, the most recent achievements regarding ILCs subsets including new classifications, their transcription factors, markers, cytokine release and mechanisms that led to either progression or inhibition of many tumors have been evaluated. Additionally, the available data regarding ILCs in most prevalent cancers and new therapeutic approaches are summarized.

show abstract

A Novel Pro-Angiogenic Function for Interferon-γ–Secreting Natural Killer Cells

Abstract: A novel pro-angiogenic function for interferon-c-secreting natural killer cells. Invest Ophthalmol Vis Sci.

Cited by 37 publications

References 28 publications

Proangiogenic Function of T Cells in Corneal Transplantation

Proangiogenic Function of T Cells in Corneal Transplantation

CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13

Progression or suppression: Two sides of the innate lymphoid cells in cancer

Contact Info

Product

Resources

About