Interferons and Dry Eye in Sjögren’s Syndrome

Ogawa, Yoko; Shimizu, Eisuke; Ohta, Michio

doi:10.3390/ijms19113548

Cited by 43 publications

(37 citation statements)

References 68 publications

(99 reference statements)

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“…IL-33 expression is upregulated in the salivary glands of pSS patients and acts synergistically with IL-12 and IL-23 to stimulate IFN-γ secretion by NK cells, which contributes to pSS pathogenesis (72,73). The overexpression of IL-12 in SS was also shown to participate in the differentiation of helper T (Th)1 cells and IFN-γ production (74,75); and activation of IFN signaling and the recruitment of pDCs to the salivary glands of pSS patients may promote NK cell activation and IFN-γ production, thereby aggravating disease pathogenesis (71,76,77).…”

Section: Nk Cells and Sjögren's Syndromementioning

confidence: 99%

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

2021

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Autoimmune diseases generally result from the loss of self-tolerance (i.e., failure of the immune system to distinguish self from non-self), and are characterized by autoantibody production and hyperactivation of T cells, which leads to damage of specific or multiple organs. Thus, autoimmune diseases can be classified as organ-specific or systemic. Genetic and environmental factors contribute to the development of autoimmunity. Recent studies have demonstrated the contribution of innate immunity to the onset of autoimmune diseases. Natural killer (NK) cells, which are key components of the innate immune system, have been implicated in the development of multiple autoimmune diseases such as systemic lupus erythematosus, type I diabetes mellitus, and autoimmune liver disease. However, NK cells have both protective and pathogenic roles in autoimmunity depending on the NK cell subset, microenvironment, and disease type or stage. In this work, we review the current knowledge of the varied roles of NK cell subsets in systemic and organic-specific autoimmune diseases and their clinical potential as therapeutic targets.

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Section: Nk Cells and Sjögren's Syndromementioning

confidence: 99%

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

2021

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“…Pro-inflammatory cytokines are known to promote lacrimal gland destruction (in a CD25 knockout model of Sjogren’s syndrome), goblet cell loss, keratinization of the conjunctival epithelium, as well as its apoptosis (in a dry eye mouse model), and tear film instability, all potentially aggravating DED [ 60 , 61 ]. Cytokines are also detected in the tear film and conjunctival epithelium obtained from DED patients, inducing inflammation of the ocular surface [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

et al. 2021

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Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.

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“…On the basis of vast array of clinical presentation and pathological findings it is assumed that IFN expression pattern will vary among individuals and the systemic IFN type I and type II signature will influence the severity of disease. [36][37][38][39] IFN-γ is the key interferon involved in most of the pathways that have been identified in the pathogenic processes of Sjogren's syndrome. 29 It has been suggested that genetic associations of SS include, interferon regulatory factor-5 (IRF-5) and the IFN signalling pathway.…”

Section: Role Of Interferon In Ded Associated With Pssmentioning

confidence: 99%

“…29 It has been suggested that genetic associations of SS include, interferon regulatory factor-5 (IRF-5) and the IFN signalling pathway. [36][37][38]40 IL-1β and IFN-γ play a pivotal role in squamous metaplasia of the ocular surface epithelium in response to chronic inflammation. 36 Th1 cells and NK cells infiltrate at the ocular surface and release IFN-γ during the process of squamous metaplasia and as result of which both the cytokines are seen at the ocular surface in dry eyes.…”

Section: Role Of Interferon In Ded Associated With Pssmentioning

confidence: 99%

Dry eye disease associated with Primary Sjogren syndrome: An update

Maurya

Singh²,

Manisha³

et al. 2021

IJCEO

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Primary Sjögren’s syndrome (pSS) is a chronic, multisystem autoimmune disorder, characterized by mononuclear infiltration of exocrine glands and other organs, resulting in dry eye, dry mouth and extra-glandular systemic findings. Primary Sjögren syndrome is of particular interest to ophthalmologists as it constitutes an important differential diagnosis in conditions with dry eye disease. The ocular tests are of great importance for diagnosis and monitoring of primary sjogren’s syndrome. Also a better understanding of immunological mechanisms and molecular pathways have resulted in discovery of new therapeutics for local and systemic treatment. This article illustrates an update regarding pathogenesis, diagnosis, investigative procedures and treatment options for dry eye related to Sjogren’s syndrome.

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Interferons and Dry Eye in Sjögren’s Syndrome

Cited by 43 publications

References 68 publications

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

Dry eye disease associated with Primary Sjogren syndrome: An update

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