Features of ectopic lymphoid-like structures in human uveitis

Epps, Simon; Coplin, Natalie; Luthert, Philip J; Dick, Andrew D.; Coupland, Sarah E.; Nicholson, Lindsay B.

doi:10.1016/j.exer.2019.107901

Cited by 13 publications

(12 citation statements)

References 44 publications

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“…These plasma cells would not be detected by flow cytometry utilizing anti-CD19, but would still express luciferase due to the permanent removal of the stop signal after CD19-cre mediated recombination. The role of B cells in human disease and animal models of uveitis is not well studied or understood 37 , but recent reports have identified ectopic lymphoid structures that are rich in B cells in both human and animal models of EAU [38][39][40][41] . Our data suggests that the CD19-cre:ROSA-LUC could be a useful tool for studying B cells dynamics in the EAU model.…”

Section: Discussionmentioning

confidence: 99%

Bioluminescence for in vivo detection of cell-type-specific inflammation in a mouse model of uveitis

John

Rolnick

Wilson

et al. 2020

Sci Rep

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This study reports the use of cell-type-specific in vivo bioluminescence to measure intraocular immune cell population dynamics during the course of inflammation in a mouse model of uveitis. Transgenic lines expressing luciferase in inflammatory cell subsets (myeloid cells, T cells, and B cells) were generated and ocular bioluminescence was measured serially for 35 days following uveitis induction. Ocular leukocyte populations were identified using flow cytometry and compared to the ocular bioluminescence profile. Acute inflammation is neutrophilic (75% of ocular CD45 + cells) which is reflected by a significant increase in ocular bioluminescence in one myeloid reporter line on day 2. By day 7, the ocular T cell population increases to 50% of CD45 + cells, leading to a significant increase in ocular bioluminescence in the T cell reporter line. While initially negligible (< 1% of CD45 + cells), the ocular B cell population increases to > 4% by day 35. This change is reflected by a significant increase in the ocular bioluminescence of the B cell reporter line starting on day 28. Our data demonstrates that cell-type-specific in vivo bioluminescence accurately detects changes in multiple intraocular immune cell populations over time in experimental uveitis. This assay could also be useful in other inflammatory disease models.

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Section: Discussionmentioning

confidence: 99%

Bioluminescence for in vivo detection of cell-type-specific inflammation in a mouse model of uveitis

John

Rolnick

Wilson

et al. 2020

Sci Rep

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“… 22 Likewise, B-cell inflammatory infiltrates have been demonstrated in aqueous samples and chorioretinal biopsies from patients with active uveitis, 6 , 23 and lymph node–like follicles can be found in the eyes of some patients with persistent uveitis. 24 Hence, similar immune cell populations (CD4 + Th1 and Th17 cells, CD8 + cytotoxic T cells, Tregs, B cells, macrophages, and NK cells) and cytokines (TNF, IFNγ, IL-2, IL-6, IL-10, IL-12, IL-17, and IL-21/22/23) are involved in the pathogenesis of MS and uveitis (summarized in figures 1 and 2 ).…”

Section: Common Pathways In the Pathogenesis Of Ms And Iumentioning

confidence: 97%

Intermediate uveitis associated with MS

Abraham

Nicholson

Dick

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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Uveitis is a major cause of visual impairment and blindness among working-age adults, accounting for 10% of legal blindness in the United States. Among people with MS, the prevalence of uveitis is 10 times higher than among the general population, and because MS and uveitis share similar genetic risk factors and immunologic effector pathways, it is not clear whether uveitis is one of the manifestations of MS or a coincident disorder. This uncertainty raises several diagnostic and management issues for clinicians who look after these patients, particularly with regard to recognizing visual symptoms resulting from demyelination, intraocular inflammation, or the visual complications of disease modifying drugs for MS, e.g., fingolimod. Likewise, management decisions regarding patients with uveitis are influenced by the risk of precipitating or exacerbating episodes of demyelination, e.g., following anti–tumor necrosis factor biologic therapy, and other neurologic complications of immunosuppressive treatments for uveitis. In this review, we explore the similarities in the pathophysiology, clinical features, and treatment of patients with uveitis and MS. Based on the latest evidence, we make a set of recommendations to help guide neurologists and ophthalmologists to best manage patients affected by both conditions.

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“…Inflammatory cell aggregates have been reported in the ciliary body of monkeys treated with biologics, 97 at injection sites for intravitreal therapeutics, 101,102 and in experimental and spontaneous autoimmune uveitis. [103][104][105] In the limbus of rats after corneal allograft transplantation, CALT and infiltrates of mixed leukocytes extending to the limbus were suggested as a point of entry for leukocytes trafficking into the conjunctiva. 58 The importance of the uveal tract to the immunology of the eye is demonstrated by the presence of plasma cells in uveal lymphoid foci, 98 a rich network of macrophages and DCs as APC in the iris and ciliary body, 106 and the ciliary body is also a site of immune-complex deposition.…”

Section: Ocular Lymphoid Tissue Aggregates Not Associated With Mucosamentioning

confidence: 99%

“…101 T and B cells are also persistently increased in the uveal tract with experimental autoimmune uveitis, and uveal and sometimes retinal secondary lymphoid follicles are reported with recurrent spontaneous autoimmune uveitis in mice, 104 horses, 108 and humans. 105 When lymphocytic foci and secondary follicles develop in association with inflammation of the uveal tract and outer eye, a diagnosis of TLS may be more appropriate. 2,95,102,105,108,109 Otic-Associated Lymphoid Tissue…”

Section: Ocular Lymphoid Tissue Aggregates Not Associated With Mucosamentioning

confidence: 99%

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Mucosa-Associated Lymphoid Tissue and Tertiary Lymphoid Structures of the Eye and Ear in Laboratory Animals

Schuh¹

2020

Toxicol Pathol

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Mucosa-associated lymphoid tissue (MALT) of special senses is poorly described and can be confused with nonspecific mononuclear cell infiltrates and tertiary lymphoid structures (TLS). In the eye, MALT consists mostly of conjunctiva-associated lymphoid tissue (CALT) and lacrimal drainage-associated lymphoid tissue (LDALT). In humans, CALT and LDALT are important components of the normal eye-associated lymphoid tissue (EALT), but EALT is less frequently described in ocular tissues of animals. The EALT are acquired postnatally in preferential mucosal sites, expand with antigenic exposure, form well-developed lymphoid follicles, and are reported to senesce. Lymphoid follicles that are induced concurrently with chronic inflammation are more appropriately considered TLS but must be differentiated from inflammation in MALT. Less understood is the etiology for formation of lymphoid tissue aggregates in the ciliary body, limbus, or choroid of healthy eyes in animals and humans. In the healthy eustachian tube and middle ear of animals and humans, MALT may be present but is infrequently described. Concurrent with otitis media, lymphoid follicles in the eustachian tube are probably expanded MALT, but lymphoid follicles in the middle ear may be TLS. The purpose of this comparative review is to familiarize toxicologic pathologists with MALT in the special senses and to provide considerations for differentiating and reporting eye and ear MALT from immune or inflammatory cell infiltrates or inflammation in nonclinical studies, and the circumstances for reporting TLS in compartments of the eye and ear.

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Features of ectopic lymphoid-like structures in human uveitis

Cited by 13 publications

References 44 publications

Bioluminescence for in vivo detection of cell-type-specific inflammation in a mouse model of uveitis

Bioluminescence for in vivo detection of cell-type-specific inflammation in a mouse model of uveitis

Intermediate uveitis associated with MS

Mucosa-Associated Lymphoid Tissue and Tertiary Lymphoid Structures of the Eye and Ear in Laboratory Animals

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