Corneal nerve loss and increased Langerhans cells are associated with disease severity in patients with rheumatoid arthritis

Bitirgen, Gülfidan; Küçük, Adem; Ergun, Mustafa Cagri; Şatırtav, Günhal; Malik, Rayaz A.

doi:10.1038/s41433-023-02447-6

Cited by 5 publications

(5 citation statements)

References 55 publications

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“…By contrast, two studies reported worse changes in corneal nerve morphology (also by in vivo confocal microscopy) in Sjögren’s than in non-Sjögren’s syndrome DED patients(79,80). The sensitivity of corneal nerves to CD4 + T cell activation could also explain the corneal neuropathy findings that correlate with the severity of the systemic autoimmune disease in rheumatoid arthritis patients(81) or that are observed after recovery in COVID-19 patients(82).…”

Section: Discussionmentioning

confidence: 99%

CD4⁺T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model

Vereertbrugghen,

Pizzano,

Cernutto

et al. 2024

Preprint

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Dry eye disease (DED) is a disorder characterized by a dysfunctional tear film in which the corneal epithelium and its abundant nerves are affected by ocular desiccation, inflammation, and the local immune response. Although adaptive immunity and specifically CD4+ T cells play a role in DED pathogenesis, the exact contribution of these cells to corneal epithelial and neural damage remains undetermined. To address this, we explored the progression of a surgical DED model in wild-type (WT) and T cell-deficient mice. We observed that adaptive immune-deficient mice developed all aspects of DED comparably to WT mice except for the absence of functional and morphological corneal nerve changes, nerve damage-associated transcriptomic signature in the trigeminal ganglia, and sustained tear cytokine levels. Adoptive transfer of CD4+ T cells from DED WT mice to T cell-deficient mice reproduced corneal nerve damage but not epitheliopathy. Conversely, T cell-deficient mice reconstituted solely with naive CD4+ T cells developed corneal nerve impairment and epitheliopathy upon DED induction, thus replicating the WT DED phenotype. Collectively, our data show that while corneal neuropathy is driven by CD4+ T cells in DED, corneal epithelial damage develops independently of the adaptive immune response. These findings have implications for T cell-targeting therapies currently in use for DED.

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Section: Discussionmentioning

confidence: 99%

CD4⁺T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model

Vereertbrugghen,

Pizzano,

Cernutto

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…LCs, fibroblasts, and macrophages have been demonstrated to provide the basis for ECs behavior in the angiogenic niche during murine skin repair (26). The LCs density was positively correlated with disease activity in patients (27). Moreover, DCs maturation affects the synovial microenvironment in RA (13,17,28).…”

Section: Innate Immune Cells-dendritic Cellsmentioning

confidence: 92%

The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials

Zhao,

He,

Zhao

et al. 2023

Front. Immunol.

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Angiogenesis plays a key role in the pathological process of inflammation and invasion of the synovium, and primarily drives the progression of rheumatoid arthritis (RA). Recent studies have demonstrated that the Notch signaling may represent a new therapeutic target of RA. Although the Notch signaling has been implicated in the M1 polarization of macrophages and the differentiation of lymphocytes, little is known about its role in angiogenesis in RA. In this review, we discourse the unique roles of stromal cells and adipokines in the angiogenic progression of RA, and investigate how epigenetic regulation of the Notch signaling influences angiogenesis in RA. We also discuss the interaction of the Notch-HIF signaling in RA’s angiogenesis and the potential strategies targeting the Notch signaling to improve the treatment outcomes of RA. Taken together, we further suggest new insights into future research regarding the challenges in the therapeutic strategies of RA.

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“…28 Similar finding was noted when examining individuals with rheumatoid arthritis. 29 The demonstration of corneal inflammation and nerve changes in other rheumatological diseases further implicates inflammation in the structural and functional nerve changes seen in SS.…”

Section: Some Individuals With Sjo ¨Gren Syndrome Have An Ocular Phen...mentioning

confidence: 96%

Rethinking Sjögren Beyond Inflammation: Considering the Role of Nerves in Driving Disease Manifestations

Sanchez,

Dobzinski,

Fox

et al. 2024

Eye &Amp; Contact Lens: Science &Amp; Clinical Practice

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Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease characterized by destruction of mucosal glands resulting in dry eye and dry mouth. Ocular presentations can be heterogenous in SS with corneal nerves abnormalities that are structural, functional, or both. Some individuals present with corneal hyposensitivity, with a phenotype of decreased tear production and epithelial disruption. Others present with corneal hypersensitivity, with a phenotype of neuropathic pain including light sensitivity and pain out of proportion to signs of tear dysfunction. A similar correlate can be found outside the eye, with dry mouth predominating in some individuals while pain conditions predominate in others. Understanding how nerve status affects SS phenotype is an important first step to improving disease management by targeting nerve abnormalities, as well as inflammation.

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Corneal nerve loss and increased Langerhans cells are associated with disease severity in patients with rheumatoid arthritis

Cited by 5 publications

References 55 publications

CD4⁺T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model

CD4⁺T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model

The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials

Rethinking Sjögren Beyond Inflammation: Considering the Role of Nerves in Driving Disease Manifestations

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Corneal nerve loss and increased Langerhans cells are associated with disease severity in patients with rheumatoid arthritis

Cited by 5 publications

References 55 publications

CD4+T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model

CD4+T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model

The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials

Rethinking Sjögren Beyond Inflammation: Considering the Role of Nerves in Driving Disease Manifestations

Contact Info

Product

Resources

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CD4⁺T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model

CD4⁺T cells drive corneal nerve damage but not epitheliopathy in an acute aqueous-deficient dry eye model