Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration

Chen, Jiajia; Wang, Wenzhan; Li, Qiuming

doi:10.1159/000484907

Cited by 28 publications

(19 citation statements)

References 27 publications

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“…The finding on Th1 cells is supported by Chen et al who showed increased levels of IFN-γ and IL-17-expressing CD4 + T cells in the circulation of wet AMD patients when compared to control subjects (64). Th1 and Th17 cells isolated from patients also shifted monocytes toward a pro-inflammatory M1 macrophage phenotype that has been associated with retinal damage (64). In addition to data implying systemic activation of adaptive immunity, in an experimental model of AMD, cytotoxic CD8 + T cells directly facilitated RPE degeneration following the immunization of mice with carboxyethylpyrrole (CEP)-modified albumin in complete Freund's adjuvant (65).…”

Section: Adaptive Immunity In Amd Patientsmentioning

confidence: 57%

“…In a small study by Yu et al, higher levels of IFN-γ and IL-4 were measured from PHAstimulated PBMC cultures of wet AMD patients in comparison to control subjects, suggesting reactivity of Th1 and Th2 cells in patients (63). The finding on Th1 cells is supported by Chen et al who showed increased levels of IFN-γ and IL-17-expressing CD4 + T cells in the circulation of wet AMD patients when compared to control subjects (64). Th1 and Th17 cells isolated from patients also shifted monocytes toward a pro-inflammatory M1 macrophage phenotype that has been associated with retinal damage (64).…”

Section: Adaptive Immunity In Amd Patientsmentioning

confidence: 87%

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Potential Role of Myeloid-Derived Suppressor Cells (MDSCs) in Age-Related Macular Degeneration (AMD)

Kauppinen

Salminen

2020

Front. Immunol.

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Myeloid cells, such as granulocytes/neutrophils and macrophages, have responsibilities that include pathogen destruction, waste material degradation, or antigen presentation upon inflammation. During persistent stress, myeloid cells can remain partially differentiated and adopt immunosuppressive functions. Myeloid-derived suppressor cells (MDSCs) are primarily beneficial upon restoring homeostasis after inflammation. Because of their ability to suppress adaptive immunity, MDSCs can also ameliorate autoimmune diseases and semi-allogenic responses, e.g., in pregnancy or transplantation. However, immunosuppression is not always desirable. In certain conditions, such as cancer or chronically inflamed tissue, MDSCs prevent restorative immune responses and thereby aggravate disease progression. Age-related macular degeneration (AMD) is the most common disease in Western countries that severely threatens the central vision of aged people. The pathogenesis of this multifactorial disease is not fully elucidated, but inflammation is known to participate in both dry and wet AMD. In this paper, we provide an overview about the potential role of MDSCs in the pathogenesis of AMD.

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Section: Adaptive Immunity In Amd Patientsmentioning

confidence: 57%

Section: Adaptive Immunity In Amd Patientsmentioning

confidence: 87%

Potential Role of Myeloid-Derived Suppressor Cells (MDSCs) in Age-Related Macular Degeneration (AMD)

Kauppinen

Salminen

2020

Front. Immunol.

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“…The wet (neovascular) form is less frequent but is responsible for 90% of acute blindness due to AMD, which is characterized by choroidal neovascularization (CNV) with intraretinal or subretinal leakage, hemorrhage, and RPE detachments (Velez-Montoya et al 2013). Recent studies provided supporting evidence that inflammatory components and pathways might play crucial roles in the etiology of AMD (Ding et al 2009;Chan and Ardeljan 2014;Chen et al 2017).…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

“…Besides, significantly higher levels of IFN-γ and IL-17 expression by CD4+ T cells were detected in the patients of AMD. A possible mechanism is that the Th17 cells promoted monocytes toward M1 macrophage polar-ization, which was associated with retinal damage (Chen et al 2017).…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

Interleukin-17: The Role for Pathological Angiogenesis in Ocular Neovascular Diseases

Yuan-jun

Zhou

2019

Tohoku J. Exp. Med.

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Ocular neovascular diseases are featured by abnormal angiogenesis in the eye, and they seriously threaten the human visual health. These diseases include proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), retinopathy of prematurity (ROP), and retinal vein occlusion (RVO). In fact, ocular neovascular diseases represent the leading causes of vision impairment and blindness worldwide. Ocular neovascularization, the process of pathological vessel formation in eye, underlies ocular neovascular diseases. Cytokines have important regulatory roles in neovascularization through immunological networks. Interleukin (IL)-17, the signature cytokine produced by T helper 17 (Th17) cells, has proven to be involved in ocular neovascularization. However, roles of IL-17 in ocular neovascular diseases still remain controversial. This review provides an overview of the functional roles of IL-17 in ocular neovascular diseases from basic research to clinical evidence by focusing on PDR, AMD, ROP, and RVO. The possible roles of IL-17 in neovascularization are achieved through a regulatory network of cytoskeleton remodeling, vascular endothelial growth factor (VEGF), VEGF-related cytokines, and complement components. Current applications as well as potential therapies targeting IL-17 with genome editing systems are also outlined and discussed. Targeting IL-17 might be a promising therapeutic strategy against ocular neovascular diseases.

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“…Furthermore, it has been shown that tolerized T cells can inhibit further antigen presentation events and suppress the proliferation of other T cells in an antigenspecific fashion [21,22]. Conversely, effector T cells (particularly Th1 and Th17 cells) can activate APCs (including microglia) to a pro-inflammatory state [23][24][25][26]. Therefore, an IL-10 cascade in the axotomized FMNuc could reflect a mechanism regulating autoimmune responses to neuronal self-antigen released after FNA.…”

Section: Introductionmentioning

confidence: 99%

CD4+ T cell expression of the IL-10 receptor is necessary for facial motoneuron survival after axotomy

Runge

Iyer

Setter

et al. 2020

J Neuroinflammation

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Background: After peripheral nerve transection, facial motoneuron (FMN) survival depends on an intact CD4+ T cell population and a central source of interleukin-10 (IL-10). However, it has not been determined previously whether CD4+ T cells participate in the central neuroprotective IL-10 cascade after facial nerve axotomy (FNA). Methods: Immunohistochemical labeling of CD4+ T cells, pontine vasculature, and central microglia was used to determine whether CD4+ T cells cross the blood-brain barrier and enter the facial motor nucleus (FMNuc) after FNA. The importance of IL-10 signaling in CD4+ T cells was assessed by performing adoptive transfer of IL-10 receptor beta (IL-10RB)-deficient CD4+ T cells into immunodeficient mice prior to injury. Histology and qPCR were utilized to determine the impact of IL-10RB-deficient T cells on FMN survival and central gene expression after FNA. Flow cytometry was used to determine whether IL-10 signaling in T cells was necessary for their differentiation into neuroprotective subsets. Results: CD4+ T cells were capable of crossing the blood-brain barrier and associating with reactive microglial nodules in the axotomized FMNuc. Full induction of central IL-10R gene expression after FNA was dependent on CD4+ T cells, regardless of their own IL-10R signaling capability. Surprisingly, CD4+ T cells lacking IL-10RB were incapable of mediating neuroprotection after axotomy and promoted increased central expression of genes associated with microglial activation, antigen presentation, T cell co-stimulation, and complement deposition. There was reduced differentiation of IL-10RB-deficient CD4+ T cells into regulatory CD4+ T cells in vitro. Conclusions: These findings support the interdependence of IL-10-and CD4+ T cell-mediated mechanisms of neuroprotection after axotomy. CD4+ T cells may potentiate central responsiveness to IL-10, while IL-10 signaling within CD4+ T cells is necessary for their ability to rescue axotomized motoneuron survival. We propose that loss of IL-10 signaling in CD4+ T cells promotes non-neuroprotective autoimmunity after FNA.

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Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration

Cited by 28 publications

References 27 publications

Potential Role of Myeloid-Derived Suppressor Cells (MDSCs) in Age-Related Macular Degeneration (AMD)

Potential Role of Myeloid-Derived Suppressor Cells (MDSCs) in Age-Related Macular Degeneration (AMD)

Interleukin-17: The Role for Pathological Angiogenesis in Ocular Neovascular Diseases

CD4+ T cell expression of the IL-10 receptor is necessary for facial motoneuron survival after axotomy

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