Characterization of Effector T Cells in Dry Eye Disease

Annan, Jaafar El; Chauhan, Sunil; Ecoiffier, Tatiana; Zhang, Qiang; Saban, Daniel R.; Dana, Reza

doi:10.1167/iovs.08-2417

Cited by 135 publications

(116 citation statements)

References 39 publications

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“…A majority of the experimental studies investigating the immunopathogenesis of DED have used a combination of desiccating environmental stress (e.g., CEC) and pharmacologic tear inhibition (e.g., SCP) to induce murine DED. [4][5][6][7][8][9] A previous study showed that SCP not only reduced lacrimal secretion, but induced lacrimal gland inflammation. 24 Given the potential effects of SCP on immune responses, it is vital to determine the effects of mAChR blockade on pathogenic immune responses in this model of experimental DED.…”

Section: Discussionmentioning

confidence: 99%

“…These findings are consistent with previous studies that combined desiccating stress (e.g., CEC) and SCP-induced DED. [5][6][7] However, immune responses in the draining CLN of CEC and SCP-induced models differ (Fig. 7).…”

Section: Discussionmentioning

confidence: 99%

“…5,6 Therefore, distant inguinal lymph nodes (ILN) were selected to determine the systemic effects of SCP on CD4 þ T-cells. After 14 days of DED induction, ILN were harvested and examined using flow cytometry to measure T-cell frequency and ELISA to measure cytokine production.…”

Section: Cec and Scp-induced Ded Exhibit Comparable Th1 Responsesmentioning

confidence: 99%

“…3 Experimental evidence suggests that DED is an immunoinflammatory disorder of the ocular surface that involves effector Th-cell responses and regulatory T-cell (Treg) dysfunction. [4][5][6][7] An experimental model used commonly to study the immunopathogenesis of DED utilizes a combination of desiccating environmental stress and pharmacologic inhibition of aqueous tear secretion. 4,8,9 Desiccating environmental conditions are produced using either an air blower or a controlled-environment chamber (CEC) that allows for the continuous regulation of environmental conditions, such as temperature, humidity, and airflow.…”

mentioning

confidence: 99%

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Effect of Desiccating Environmental Stress Versus Systemic Muscarinic AChR Blockade on Dry Eye Immunopathogenesis

Chen

Chauhan

Lee

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. A majority of experimental data on dry eye disease (DED) immunopathogenesis have been derived from a murine model of DED that combines desiccating environmental stress with systemic muscarinic acetylcholine receptor (mAChR) inhibition. However, to our knowledge the effects of pharmacologic mAChR blockade on the pathogenesis of experimental DED have not been evaluated systemically. The purpose of our study was to investigate the differential effects of desiccating environmental stress and mAChR inhibition on the pathogenesis of DED.METHODS. DED was induced in female C57BL/6 mice by exposure to a desiccating environment in the controlled-environment chamber or to systemic scopolamine, or by performing extraorbital lacrimal gland excision. Clinical disease was assessed using corneal fluorescein staining (CFS) and the cotton thread test (CTT). Corneal CD11b þ and conjunctival CD3 þ T-cell infiltration were evaluated by flow cytometry. T-cells from draining cervical lymph nodes (CLN) and distant inguinal lymph nodes (ILN) were analyzed for Th1, Th2, Th17, and Treg responses by flow cytometry and ELISA.RESULTS. Desiccating environmental stress and systemic mAChR blockade induced similar clinical signs of DED. However, desiccating environmental stress imparted higher conjunctival CD3 þ T-cell infiltration, and greater Th17-cell activity and Treg dysfunction than mAChR blockade, while mAChR blockade decreased tear secretion to a greater extent than desiccating environmental stress. Systemic mAChR blockade attenuated Th17 activity and enhanced Th2 and Treg responses without affecting Th1 activity. CONCLUSIONS. In vivo inhibition of mAChRs variably affects CD4þ T-cell subsets, and desiccating environmental stress and systemic mAChR blockade induce DED through different primary pathogenic mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cec and Scp-induced Ded Exhibit Comparable Th1 Responsesmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Effect of Desiccating Environmental Stress Versus Systemic Muscarinic AChR Blockade on Dry Eye Immunopathogenesis

Chen

Chauhan

Lee

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…After activation, Th cells can differentiate into Th-1, Th-2, Th-3, and Th-17 subtypes. Studies have shown that Th-1 and Th-17 cells are correlated with the pathogenesis of dry eye (Stern et al, 2005;Yoon et al, 2007;De Paiva et al, 2009;El Annan et al, 2009;Zheng et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye

Hsu¹,

Lee²,

Chang³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Thyroid orbitopathy (TO) is an autoimmune disease that is complicated by ocular surface disorders, leading to discomfort. Dry eye is very prevalent in patients with TO. Recent studies on the pathogenesis of dry eye have focused on the inflammatory process, and some supporting evidence has been discovered. Because TO is a disorder of autoimmune origin, we assumed that the association between TO and dry eye is related to inflammation. Inflammation of the ocular surface in TO-related dry eye has not been well studied. In this study, we assessed cellular inflammation of the ocular surface and the cytokine profiles in patients with TO-related dry eye. Conjunctival impression cytology (CIC) was assessed with an immunofluorescent assay. TO-related dry eye was diagnosed by using the Schirmer test, tear break-up time, thyroid function, and clinical signs. CIC was combined with immunological staining of interleukin-1a (IL-1a), IL-1b, and IL-6. The immunological impression cytology (IC) grade was compared to the clinical activity score of TO. All TO patients with dry eye were positive for IL-1a, IL-1b, and IL-6. However, the normal controls were also positive for IL-1a. A trend was observed between the clinical inflammatory score and immunological IC grade. This study was the first to delineate the immunological IC of TO-related dry eye. Our study aimed to investigate the pathogenesis of dry eye in TO. Our findings suggest that the conjunctival cytokines IL-1a, IL-1b, and IL-6 may play a role. The results of this study will be useful for future studies of additional inflammatory cytokines, and the levels of these cytokines could be used as an outcome to assess the efficacy of treatment, such as anti-cytokine or immunosuppression therapy, in patients with TOrelated dry eye or other ocular surface inflammatory disorders.

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Evidence of Corneal Lymphangiogenesis in Dry Eye Disease

et al. 2010

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To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model. Methods: Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b ϩ /LYVE-1 ϩ monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class II hi ) antigen-presenting cells to the lymphoid compartment.Results: Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (PϽ.001) and lymphatic caliber (PϽ.02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b ϩ /LYVE-1 ϩ monocytic cells to the cornea and homing of mature CD11b ϩ antigen-presenting cells to the draining lymph nodes were also associated with DED. Conclusion:Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.

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Characterization of Effector T Cells in Dry Eye Disease

Cited by 135 publications

References 39 publications

Effect of Desiccating Environmental Stress Versus Systemic Muscarinic AChR Blockade on Dry Eye Immunopathogenesis

Effect of Desiccating Environmental Stress Versus Systemic Muscarinic AChR Blockade on Dry Eye Immunopathogenesis

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye

Evidence of Corneal Lymphangiogenesis in Dry Eye Disease

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