Interferon-α2a induces CD4+ T cell apoptosis and suppresses Th1/Th17 responses via upregulating IRF1-mediated PDL1 expression in dendritic cells from Behcet’s uveitis

Zhu, Yunyun; Yu, Qiuyue; Su, Guannan; Shao, Ningsheng; Feng, Jie; Luo, Xiang; Zhou, Chunjiang; Yang, Peizeng

doi:10.1016/j.clim.2023.109303

Cited by 9 publications

(3 citation statements)

References 47 publications

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“…The expression of programmed death ligand-1 (PDL1) and its transcription factor interferon regulatory factor I (IRF1) in DCs from active BU patients has been found to be decreased in recent studies. This decrease in expression is observed to correlate with the level of disease activity [ 109 ]. Confocal imaging studies consistently demonstrate an increased density of DCs in the corneas of BU patients, regardless of disease severity [ 110 ].…”

Section: Etiology and Pathogenesismentioning

confidence: 99%

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Decoding Behcet’s Uveitis: an In-depth review of pathogenesis and therapeutic advances

Guan,

Li,

et al. 2024

J Neuroinflammation

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Behcet’s disease (BD) is a rare but globally distributed vasculitis that primarily affects populations in the Mediterranean and Asian regions. Behcet’s uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients. BU is characterized by bilateral, chronic, recurrent, non-granulomatous uveitis in association with complications such as retinal ischemia and atrophy, optic atrophy, macular ischemia, macular edema, and further neovascular complications (vitreous hemorrhage, neovascular glaucoma). Although the etiology and pathogenesis of BU remain unclear, numerous studies reveal that genetic factors (such as HLA-B51), dysregulated immune responses of both the innate and adaptive immune systems, infections (such as streptococcus), and environmental factors (such as GDP) are all involved in its development. Innate immunity, including hyperactivity of neutrophils and γδT cells and elevated NK1/NK2 ratios, has been shown to play an essential role in this disease. Adaptive immune system disturbance, including homeostatic perturbations, Th1, Th17 overaction, and Treg cell dysfunction, is thought to be involved in BU pathogenesis. Treatment of BU requires a tailored approach based on the location, severity of inflammation, and systemic manifestations. The therapy aims to achieve rapid inflammation suppression, preservation of vision, and prevention of recurrence. Systemic corticosteroids combined with other immunosuppressive agents have been widely used to treat BU, and beneficial effects are observed in most patients. Recently, biologics have been shown to be effective in treating refractory BU cases. Novel therapeutic targets for treating BU include the LCK gene, Th17/Treg balance, JAK pathway inhibition, and cytokines such as IL-17 and RORγt. This article summarizes the recent studies on BU, especially in terms of pathogenesis, diagnostic criteria and classification, auxiliary examination, and treatment options. A better understanding of the significance of microbiome composition, genetic basis, and persistent immune mechanisms, as well as advancements in identifying new biomarkers and implementing objective quantitative detection of BU, may greatly contribute to improving the adequate management of BU patients.

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Section: Etiology and Pathogenesismentioning

confidence: 99%

“…Moreover, IFNα stimulated IL-10 secretion by CD4 + T cells in BU patients, which then hindered IL-17 secretion by PBMCs. In conclusion, the therapeutic benefits of IFNα-2a in BU are mediated by dendritic cells and CD4 + T cells [ 109 ].…”

Section: Advances In Therapiesmentioning

confidence: 99%

Decoding Behcet’s Uveitis: an In-depth review of pathogenesis and therapeutic advances

Guan,

Li,

et al. 2024

J Neuroinflammation

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“…The culture of human peripheral blood DC was carried out according to the previous protocol (25)(26)(27). Upon receiving informed consent, peripheral blood was collected from patients with DR and DM, as well as from healthy volunteers, into tubes containing EDTA-K2.…”

Section: Cell Isolation and Culturementioning

confidence: 99%

NECA alleviates inflammatory responses in diabetic retinopathy through dendritic cell toll-like receptor signaling pathway

Li,

Chen,

Wang

et al. 2024

Front. Immunol.

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IntroductionThis study examined the impact of 5’-(N- ethylcarboxamido)adenosine (NECA) in the peripheral blood of healthy individuals, those with diabetes mellitus, diabetic retinopathy (DR), and C57BL/6 mice, both in vivo and in vitro.MethodsEnzyme-linked immunosorbent assay (ELISA) and flow cytometry (FCM) were used to evaluate the effects of NECA on dendritic cells (DCs) and mouse bone marrow-derived dendritic cells (BMDCs) and the effects of NECA-treated DCs on Treg and Th17 cells. The effect of NECA on the Toll-like receptor (TLR) pathway in DCs was evaluated using polymerase chain reaction (PCR) and western blotting (WB).ResultsFCM and ELISA showed that NECA inhibited the expression of surface markers of DCs and BMDCs, increased anti-inflammatory cytokines and decreased proinflammatory cytokines. PCR and WB showed that NCEA decreased mRNA transcription and protein expression in the TLR-4-MyD88-NF-kβ pathway in DCs and BMDCs. The DR severity in streptozocin (STZ) induced diabetic mice was alleviated. NECA-treated DCs and BMDCs were co-cultivated with CD4+T cells, resulting in modulation of Treg and Th17 differentiation, along with cytokine secretion alterations.ConclusionNECA could impair DCs’ ability to present antigens and mitigate the inflammatory response, thereby alleviating the severity of DR.

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Behçet's Disease: From Bench To Bedside

Sawalha

Direşkeneli

2023

Clinical Immunology

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Interferon-α2a induces CD4+ T cell apoptosis and suppresses Th1/Th17 responses via upregulating IRF1-mediated PDL1 expression in dendritic cells from Behcet’s uveitis

Cited by 9 publications

References 47 publications

Decoding Behcet’s Uveitis: an In-depth review of pathogenesis and therapeutic advances

Decoding Behcet’s Uveitis: an In-depth review of pathogenesis and therapeutic advances

NECA alleviates inflammatory responses in diabetic retinopathy through dendritic cell toll-like receptor signaling pathway

Behçet's Disease: From Bench To Bedside

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