Kinetics of immune cell migration at the human ocular surface

Chan, Joanna Shi-En; Amankwah, R; Robins, R. A.; Gray, Trevor; Dua, Harminder S.

doi:10.1136/bjo.2007.131003

Cited by 10 publications

(5 citation statements)

References 22 publications

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“…In addition to its anit-inflammatory properties, epithelial cell-derived TGF-β (85) can also induce MMP-9 production [110–112] during desiccating stress, and may also contribute to fibrosis on the ocular surface. Furthermore, there are several types of resident cells, including macrophages, DCs, γδ T cells, and infiltrating innate cells, such as natural killer (NK) cells and monocytes that act in concert to potentiate the innate response, cause direct tissue damage, and coordinate the chronic antigen-driven autoimmune response [106,113,114]. The pathogenic role of these innate cell types in dry eye is now being realized.…”

Section: Innate Immune Responsementioning

confidence: 99%

Dry Eye as a Mucosal Autoimmune Disease

Stern

Schaumburg

Pflugfelder

2013

International Reviews of Immunology

295

232

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Dry eye is a common ocular surface inflammatory disease that significantly affects quality of life. Dysfunction of the lacrimal function unit (LFU) alters tear composition and breaks ocular surface homeostasis, facilitating chronic inflammation and tissue damage. Accordingly, the most effective treatments to date are geared towards reducing inflammation and restoring normal tear film. The pathogenic role of CD4+ T cells is well known, and the field is rapidly realizing the complexity of other innate and adaptive immune factors involved in the development and progression of disease. The data support the hypothesis that dry eye is a localized autoimmune disease originating from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface.

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Section: Innate Immune Responsementioning

confidence: 99%

Dry Eye as a Mucosal Autoimmune Disease

Stern

Schaumburg

Pflugfelder

2013

International Reviews of Immunology

295

232

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“…8–12 IEL subsets in the conjunctiva that have been identified to date include CD4 + , CD8 + , and γδ + T cells and natural killer (NK) + cells. 13 …”

Section: Introductionmentioning

confidence: 99%

Homeostatic control of conjunctival mucosal goblet cells by NKT-derived IL-13

et al. 2011

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Although the effects of the interleukin 13 (IL-13) on goblet cell (GC) hyperplasia have been studied in the gut and respiratory tracts, its effect on regulating conjunctival GC has not been explored. The purpose of this study was to determine the major IL-13-producing cell type and the role of IL-13 in GC homeostasis in normal murine conjunctiva. Using isolating techniques, we identified natural killer (NK)/natural killer T (NKT) cells as the main producers of IL-13. We also observed that IL-13 knockout (KO) and signal transducer and activator of transcription 6 knockout (STAT6KO) mice had a lower number of periodic acid Schiff (PAS) + GCs. We observed that desiccating stress (DS) decreases NK population, GCs, and IL-13, whereas it increases interferon-γ (IFN-γ) mRNA in conjunctiva. Cyclosporine A treatment during DS maintained the number of NK/NKT cells in the conjunctiva, increased IL-13 mRNA in NK + cells, and decreased IFN-γ and IL-17A mRNA transcripts in NK + and NK − populations. C57BL/6 mice chronically depleted of NK/NKT cells, as well as NKT cell-deficient RAG1KO and CD1dKO mice, had fewer filled GCs than their wild-type counterparts. NK depletion in CD1dKO mice had no further effect on the number of PAS + cells. Taken together, these findings indicate that NKT cells are major sources of IL-13 in the conjunctival mucosa that regulates GC homeostasis.

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“…[ 9 ] Immunohistochemistry—Biopsy from tarsal and superior temporal bulbar conjunctiva from normal adults undergoing squint or cataract surgery Leukocytes including T cells and macrophages are present in the epithelium and substantia propria CD8 exceeds CD4 levels in the epithelium but these levels are reversed in the substantia propria Chan et al. [ 44 ] Flow cytometry—Organ cultures of human conjunctival samples, denuded of the epithelium CD4 cells preferentially migrate through intrastromal channels as compared with CD8 cells Reinoso et al. [ 10 ] Brush cytology—Inferior fornix and tarsal conjunctival cells in evaporative dry eye patients CD4/CD8 ratio decreased after dry eye treatment Power et al.…”

Section: Discussionmentioning

confidence: 99%

Conjunctival T Cell Profile in Allogeneic Hematopoietic Stem Cell Transplant Patients after Instilling Topical Cyclosporine-A 0.1% Cationic Emulsion

et al. 2023

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Introduction To profile conjunctival T cell populations in allogeneic hematopoietic stem cell transplant (HSCT) patients after instillation of daily topical cyclosporine-A (CsA) 0.1% cationic emulsion (Ikervis), and to evaluate patients’ tolerance to these eye drops. Methods Nineteen participants were prescribed Ikervis prophylaxis once daily to both eyes from 3–5 weeks pre-HSCT to 12 months post-HSCT. The outcome measure was conjunctival T cell proportions from flow cytometry after impression cytology. Covariates included visual acuity, intraocular pressure, slit lamp and fundal examination, dry eye (SPEED) and quality of life questionnaires, non-invasive keratograph tear break-up time (NIKBUT), conjunctival redness, meibography, lipid thickness, Schirmer test, tear cytokines, fluorescein staining, tear osmolarity, and meibomian gland expressibility. Results The conjunctival T cell analysis showed either stable or decreased proportions of conjunctival CD4 T cells at the last visit from baseline in compliant patients. CD4 proportions were increased in non-compliant patients and in the single patient who developed ocular graft-versus-host disease (GVHD). All patients were tolerant to Ikervis but 6/19 were not compliant. In the majority of patients, vision did not affect activities of daily living. Pre- and post-HSCT up to the last study visit, there was no statistically significant change in clinical covariates. Only one participant developed ocular GVHD at 9 months post-HSCT. Conclusion Superficial conjunctival T cell profile reflects compliance to daily topical Ikervis eye drops and clinical ocular surface parameters in allogenic HSCT patients. Tolerance is comparable to other formulations of topical CsA in the first 12 months. ClinicalTrials.gov Identifier NCT04636918. URL: https://clinicaltrials.gov/ct2/show/NCT04636918?cond=ocular+Graft+Versus+Host+Disease&cntry=SG&draw=2&rank=2 . Supplementary Information The online version contains supplementary material available at 10.1007/s40123-023-00686-0.

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Kinetics of immune cell migration at the human ocular surface

Cited by 10 publications

References 22 publications

Dry Eye as a Mucosal Autoimmune Disease

Dry Eye as a Mucosal Autoimmune Disease

Homeostatic control of conjunctival mucosal goblet cells by NKT-derived IL-13

Conjunctival T Cell Profile in Allogeneic Hematopoietic Stem Cell Transplant Patients after Instilling Topical Cyclosporine-A 0.1% Cationic Emulsion

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