Interferons and Dry Eye in Sjögren’s Syndrome DOI Open Access
Yoko Ogawa, Eisuke Shimizu, Kazuo Tsubota

и другие.

International Journal of Molecular Sciences, Год журнала: 2018, Номер 19(11), С. 3548 - 3548

Опубликована: Ноя. 10, 2018

Various cytokines, including interferon (IFN)-γ and IL-17, are augmented, autoreactive T cells B activated in the immune pathogenesis of Sjögren’s syndrome (SS). In particular, IFNs involved both early stages innate immunity by high level type I IFN glandular tissue sera later disease progression II producing through cell activating factor SS. Genetically modified mouse models for some these molecules have been reported will be discussed this review. New findings from human SS animal elucidated mechanisms underlying SS-related dry eye. We discuss IFN-γ several other that represent candidate targets treating inflammation

Язык: Английский

The Pathophysiology of Dry Eye Disease DOI
Stephen C. Pflugfelder, Cintia S. de Paiva

Ophthalmology, Год журнала: 2017, Номер 124(11), С. S4 - S13

Опубликована: Окт. 18, 2017

Язык: Английский

Процитировано

377
Sjogren’s syndrome: An update on disease pathogenesis, clinical manifestations and treatment DOI

Frederick B. Vivino,

Vatinee Y. Bunya,

Giacomina Massaro‐Giordano

и другие.

Clinical Immunology, Год журнала: 2019, Номер 203, С. 81 - 121

Опубликована: Апрель 29, 2019

Язык: Английский

Процитировано

190
Immune responses to injury and their links to eye disease DOI Creative Commons
Mary Ann Stepp, A. Sue Menko

Translational research, Год журнала: 2021, Номер 236, С. 52 - 71

Опубликована: Май 27, 2021

The eye is regarded as an immune privileged site. Since the presence of a vasculature would impair vision, located outside central light path. As result, many regions evolved mechanisms to deliver cells sites dysgenesis, injury, or in response age-related pathologies. While purpose these responses reparative protective, cytokines released by compromise visual acuity inducing inflammation and fibrosis. traumatic pathological injury distinct different eye. Age-related diseases impact both anterior posterior segment lead reduced quality life blindness. Here we focus attention on role that fibrosis play progression pathologies cornea lens well glaucoma, formation epiretinal membranes, proliferative vitreoretinopathy.

Язык: Английский

Процитировано

131
Corneal stromal repair and regeneration DOI Creative Commons
Rajiv R. Mohan, Duraisamy Kempuraj, Sharon D’Souza

и другие.

Progress in Retinal and Eye Research, Год журнала: 2022, Номер 91, С. 101090 - 101090

Опубликована: Май 29, 2022

Язык: Английский

Процитировано

120
Emerging role of gut microbiota in autoimmune diseases DOI Creative Commons
Xinyi Wang, Wei Yuan, Chunjuan Yang

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 3, 2024

Accumulating studies have indicated that the gut microbiota plays a pivotal role in onset of autoimmune diseases by engaging complex interactions with host. This review aims to provide comprehensive overview existing literatures concerning relationship between and diseases, shedding light on interplay microbiota, host immune system. Furthermore, we aim summarize impacts potential mechanisms underlie primarily focusing systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, type 1 diabetes mellitus, ulcerative colitis psoriasis. The present will emphasize clinical significance applications interventions based as innovative adjunctive therapies for diseases.

Язык: Английский

Процитировано

21
Th17 cells in primary Sjögren's syndrome: Pathogenicity and plasticity DOI Creative Commons
Gwenny M. Verstappen, Odilia B. J. Corneth, Hendrika Bootsma

и другие.

Journal of Autoimmunity, Год журнала: 2017, Номер 87, С. 16 - 25

Опубликована: Ноя. 27, 2017

Th17 cells play an important physiological role at mucosal barriers, and are involved in inflammatory responses to pathogens. their signature cytokine IL-17 also present salivary gland lesions of primary Sjögren's syndrome (pSS) patients can be elevated peripheral blood. In pSS patients, clear correlations between increased cell activity symptoms the disease have not been found, but may contribute progression, for example by supporting autoreactive B responses. mouse models pSS, pathogenesis, particularly onset, when there is a disturbed balance T effector regulatory cells. Studying pathogenicity humans complicated due plasticity this subset, allowing them obtain different functions depending on local environment. develop towards Th17.1 cells, producing both IFN-γ, or even Th1-like IFN-γ absence IL-17. These subsets more pathogenic than bona fide Co-expression has shown promote chronic inflammation several autoimmune diseases pathogenesis. line with noticeable models, interference generation, recruitment (e.g. inhibition) prevent ameliorate these models. Therapies targeting tested so far although treatment rituximab seems lower systemic protein levels, lesser extent chemokine receptor-defined review we discuss current knowledge human murine pSS. We postulate that enhance main target sites disease, i.e. lacrimal glands.

Язык: Английский

Процитировано

152
Effects of Aging in Dry Eye DOI
Cintia S. de Paiva

International Ophthalmology Clinics, Год журнала: 2017, Номер 57(2), С. 47 - 64

Опубликована: Янв. 1, 2017

Introduction Tear dysfunction is one of the most common problems encountered by eye doctors. has a reported prevalence ranging from 2% to 14.2%.1–3 It been found increase with age fourth eighth decade life and more prevalent in women than men throughout this period.4,5 results disease or components lacrimal functional unit that consists tear producing glands their neural connections. Many patients over 40 have evidence meibomian gland (MGD) as an underlying cause, particularly unstable film, but normal production volume. This review will focus on epidemiological aspects aging, possible mechanisms for age-related dry discuss some potential therapies along lessons learned animal models aging. Aging Risk Factor Dry Eye Significant Large studies Women's Health Study Physician's noted increases every 5 years after 50, greater compared men.1,3–8 Age female sex be greatest risk factors eye. supported clinical findings decreased through sixth life.9,10 The corneal surface irregularity degrades visual function decreasing contrast sensitivity acuity.11,12 presence was significantly impact ability perform daily activities such reading, using computer driving.13 Using time trade-off techniques, Schiffman et al14 calculated severe had same quality-of-life moderate angina.15 With increasing aged population increased expectancy, it expected continue main reasons ophthalmologic visits.16 Therefore, better understanding specifically tailored specific are much needed. (LG) suffers Various histopathologic changes were observed human LG acinar atrophy; periacinar fibrosis; periductal interlobular ductal dilatation; proliferation; lymphocytic infiltration; fatty infiltration.17–20 Several differences exist between palpebral orbital lobes. Diffuse fibrosis diffuse atrophy lobes frequently men.20,21 Rodents used aging research suffer aging-related similar humans (see Rocha al).22–25 Age-related eyelid alterations include lid laxity, (MG) orifice metaplasia, decrease volume break-up eye.26–31 In young healthy eyelid, MG orifices located anterior mucocutaneous junction can identified Marx's line, physiological line staining diagnostic dyes, fluorescein, lissamine green, rose bengal. migrate anteriorly aging.32 androgen receptors respond stimulation31,33–37 MGD frequent women.28,29,38,39 may occur itself association aqueous-tear deficiency (ATD). inflammatory cytokine milieu both tears conjunctiva cells collected impression cytology different ATD.40–44 ATD significant goblet cell loss, expression interferon (IFN)-γ interleukin (IL)-17A controls, none aforementioned present patients.44 Another disorder conjunctivochalasis, condition where folds becomes redundant obstruct puncta cause ocular discomfort. often associated age45–48 discussed details companion article Gumus Pflugfelder. There still controversy if leads dry-eye totally mechanism per se.49 For example, factor loss remains controversial.23,50–54 becoming apparent autoimmune eye, inflammation complex immune response overtime profound (Fig. 1).22–25,28,51,55–58Figure 1: induces systemic also unit.Age-related Comorbidities Iatrogenic accompanied co-morbidities cardiovascular diseases, type 2 diabetes, depression, glaucoma, other diseases. Some these comorbidities themselves medications manage them, deleterious secondary effect surface. An example diabetes mellitus affects retina, nerves eye.59–61 alters homeostasis required control original morbidity drying effects. antihypertensive, antihistaminics antidepressants well-recognized classes drugs surface.3,5–8,56,62 complete list aggravate please refer Fraunfelder colleagues62,63 visit National Drug registry (www.eyedrugregistry.com/about.html). Patients incidence elderly patients, complain about irritation.64,65 Although direct compounds treat glaucoma cannot excluded, benzalkonium chloride, widely eyedrop preservative due its potent antibacterial action, recognized toxic Benzalkonium chloride enhances drug penetration, partially epithelial barrier breakage toxicity epithelium.65–68 Recent shown switching preservative-free solution improved related-symptoms no efficacy antiglaucoma drugs, promising relief great number eyedrops.69–71 Possible Mechanisms Leading All organisms start soon they born. celebrated milestones (ie, first baby steps words, definitive tooth, mustache shaving boys; child, etc.), decline health status vitality accompanies nuisance many. economical burden society caregivers expectancy well susceptibility cancer, autoimmunity, frailty. system undergoes named immunosenescence, characterized naive T cells, chronic inflammation, hyperimmunoglobulinemia, poor vaccines, infections.72–75 A typical feature chronic, low-grade status, inflammaging,76 general proinflammatory cytokines. Increased serum mediators Alzheimer disease, dementia, Parkinson diabetes.76–78 consequences survival reliable predictors mortality elderly.75 Other cellular/metabolic theories regarding oxidative stress, DNA damage, alteration repair, protein glycation, telomere shortening, proteasome name few.79,80 extensive body accumulated areas, precise mechanism(s) poorly understood. Every ages, not at rate; accompany pathologic person unique so own true inflammation. last 20 there shift paradigm, merely autoimmunity play important role. levels related IL-1β, IL-6, TNF-α, IL-17, IFN-γ fluid subjects.12,40,44,81–90 activation local environment another universal HLA-DR+ finding, which indicator therapeutic trials.81,91–100 features matrix metalloproteinases (MMPs), chemokines proteins involved squamous metaplasia epithelium, endoplasmic reticulum stress.12,81,83,85,96,97,101–117 acute exacerbations when performing driving, viewing video display long periods shopping stores high flow AC. live work controlled drafty and/or low humidity (desiccating stress) environmental conditions, irritation disease118–122 experience productivity quality life.123,124 Exposure desiccating conditions activate stress-sensing cells/pathways surface, stimulate synthesize secrete cytokines MMPs detected themselves.42,85 stress sensitize nociceptors changes, breakdown tight junctions resulting dysfunction, clinically uptake fluorescein. Calonge colleagues.125 Animal Models variety described study pathogenesis model uses combination humidity, pharmacological cholinergic blockade become standard field. 65 publications since description.126 recapitulates several inclusive epithelium.127–145 mostly inbred C57BL/6 mouse strain, while Balb/c mice slightly kinetics.143 valuable tool develop MGD, staining, conjunctival infiltration dacryoadenitis.23,146,147 Similarly desiccated Sjögren Syndrome (SS) MMP-9 T-cell IFN-γ, influx CD4+ CD8+ into LG,23 suggesting multiple inciting converge produce independent initiating factor. Inflammation denominator situations. Lessons Stern Pflugfelder.148 Pathogenic utilized summarized briefly next paragraphs. Female Sex Similar studies,4,149 disruption age-matched male mice, although density sexes.23 IL-17A mice. IL-17 stimulates -3 -9, break disrupt function.85,150–153 life7,14 vision, decreases sensitivity.12,13 We speculate bring clinic men, hormones influences excluded. Aged Cells Spontaneously Autoreactive SS subjects, stressed biopsies.154–159 mice.23 Furthermore, adoptive transfer induced donors, demonstrating participate eye.23,25 These indicate promotes generation autoreactive cells; however, unknown wells antigen. system, lack peripheral tolerance exposure antigen life's period maybe play. all three could acting synergistically. Interferon-γ Participates Goblet Cell Loss goblet-cell richest tissues body, just trailing intestinal tract. very sensitive besides mucins, implicated immunomodulation surface.160–163 Th-2 signature IL-13 role homeostasis.164,165 contrast, negatively cells.112,131,159,166 DS-induced aged-induced upregulation KO resistant aged-related loss.23,57,159 Regulatory Dysfunctional variation nonobese diabetic does Coursey al25 demonstrated dacryoadenitis NOD.B10.H2b frequency regulatory (Tregs) LG, despite pathology strain. agreement reports biopsies salivary Foxp3+ correlated disease.167,168 Despite being dysfunctional unable suppress effector vitro, murine Tregs do loose expression, acquire IL-17. regs effectors resulted higher keratoconjunctivitis scores effectors, vivo suppression acquisition phenotype.25 Oxidative Stress Impairs Secretion Reactive oxygen species generated metabolism must counteracted antioxidant defenses prevent damage lipids, DNA, mitochondria. Mice mitochondrial antioxidative pathways altered homeostasis, leading volume, staining.169–172 support studies, enzymes markers patients.108–111 Elevated concentration hexanoyl-lysine, lipid marker, confocal microscopy evaluating controls.108 unclear occurs consequence Deng al173 recently showed hyperosmolarity cultured cells. MGs Become Atrophic Histologic analysis eyelids many morphologic including cystic dilatation acini ducts, acini, thickening basement membrane, granulation tissue, lipogranulomatous inflammation.26 dropout cytokines, meibocyte differentiation.145,146,174,175 postulated stem within necessary duct keratinization, Keratin 10 nor SPRR1-a MG.146,175 elegant immunofluorescent computed tomography 3-dimensional reconstruction, keratinization further corroborating findings.146 Treatment only FDA-approved Cyclosporine, modulator, extensively forms eye.92,99,106,117,176–179 Lifitegrast, novel inhibitor lymphocyte function-associated antigen-1 (LFA-1) migration vessels, received approval signs symptoms July 2016. Results phase 3 trials results.180–182 reviews current see published reviews.183–185 new reviewed nonpharmacological approach improve use supplements. Polyunsaturated acids omega-6 (linolenic acid) omega-3 (α-linolenic gained popularity oral supplements dendritic cells.95,186–190 holistic aging-dry proposed involves calorie restriction (CR) supplementation vitamins antioxidants.191 CR without malnutrition emerged 21st century strategy 1935 McCay al,192 interest prolonged span, tumors rodents.193–196 duplicated nonhuman primates,197,198 generating scientific community intervention. massive then, metabolic, hormonal molecular changes. detailed NIH-sponsored CALERIE (comprehensive assessment long-term effects reducing intake energy) trial humans, Most al.199 ophthalmology, substantially submandibular prone mice.200 TNF-α IL-6 TGF-β1 noted.200 rats, 6 months secretion, morphology oxidation 8-hydroxy-2 deoxyguanosine (8-OHdG) 4-hydroxynonenal relates stress.201 Conclusions intensive research, nature elusive. Not rate. However, biochemical, molecular, interacting. participates Understanding enable early interventions end-stage organ disease.

Язык: Английский

Процитировано

117
Immune - Goblet cell interaction in the conjunctiva DOI
Jehan Alam, Cintia S. de Paiva, Stephen C. Pflugfelder

и другие.

The Ocular Surface, Год журнала: 2020, Номер 18(2), С. 326 - 334

Опубликована: Янв. 15, 2020

Язык: Английский

Процитировано

75
Mucosal immunology of the ocular surface DOI Creative Commons
Cintia S. de Paiva, Anthony J. St. Leger, Rachel R. Caspi

и другие.

Mucosal Immunology, Год журнала: 2022, Номер 15(6), С. 1143 - 1157

Опубликована: Авг. 24, 2022

Язык: Английский

Процитировано

58
Impact of aging on the pathophysiology of dry eye disease: A systematic review and meta-analysis DOI Creative Commons
Koji Kitazawa, Takenori Inomata, Kendrick Co Shih

и другие.

The Ocular Surface, Год журнала: 2022, Номер 25, С. 108 - 118

Опубликована: Июнь 23, 2022

Язык: Английский

Процитировано

52