The B Subunit of<i>Escherichia coli</i>Heat-Labile Enterotoxin Inhibits Th1 but Not Th17 Cell Responses in Established Experimental Autoimmune Uveoretinitis

Raveney, Ben J. E.; Richards, C. M.; Aknin, Marie-Laure; Copland, David A; Burton, Bronwen R; Kerr, Emma C.; Nicholson, Lindsay B.; Williams, Neil; Dick, Andrew D.

doi:10.1167/iovs.08-1848

Cited by 17 publications

(19 citation statements)

References 51 publications

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“…After this time point, leukocyte cell numbers drop rapidly and further T cell expansion is not observed, despite the presence of high numbers of APCs and the fact that retinal damage leading to the release of autoantigens occurs (18). The infiltrating CD45…”

Section: Resultsmentioning

confidence: 99%

“…Ϫ/Ϫ ϩLy5.2 3 Ly5.2) mice were immunized with RBP-3 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] peptide to induce EAU. Control chimeric mice that received either TNFR1 Ϫ/Ϫ , (TNFR1 Ϫ/Ϫ 3 Ly5.2), or WT, (WT 3 Ly5.2), bone marrow cells were similarly immunized to allow for any effect of chimera generation on EAU induction.…”

Section: Resultsmentioning

confidence: 99%

“…Cell suspensions were acquired with a LSR-II flow cytometer (BD Cytometry Systems). Cell numbers were calculated by reference to a known standard as previously described (18). Analysis was conducted using FlowJo software (Tree Star).…”

Section: Flow Cytometry and Cell Sortingmentioning

confidence: 99%

“…Cells were harvested with a 96-well harvester, and thymidine uptake (measured in cpm) was determined by liquid scintillation with a microbeta 1450 liquid scintillation counter (Wallac). Accumulated NO production was measured in culture supernatants using Greiss reagent (Sigma-Aldrich) as previously described (18). IFN-␥, IL-17, and IL-6 productions were assessed using murine Flow cytomix kits (Bender Medsystems) according to the manufacturer's instructions.…”

Section: Cell Culture and Assessment Of Cell Functionmentioning

confidence: 99%

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TNFR1-Dependent Regulation of Myeloid Cell Function in Experimental Autoimmune Uveoretinitis

Raveney¹,

Copland

Dick

et al. 2009

The Journal of Immunology

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Experimental autoimmune uveoretinitis is an autoimmune disease induced in mice, which involves the infiltration of CD11b+ macrophages and CD4+ T cells into the normally immune-privileged retina. Damage is produced in the target organ following the activation of Th1 and Th17 T cells and by the release of cytotoxic mediators such as NO by activated macrophages. The majority of immune cells infiltrating into the retina are CD11b+ myeloid cells, but, despite the presence of these APCs, relatively limited numbers of T cells are observed in the retina during the disease course. These T cells do not proliferate when leukocytes are isolated from the retina and restimulated in vitro, although they do produce both IFN-γ and IL-17. T cell proliferation was restored by depleting the myeloid cells from the cultures and furthermore those isolated myeloid cells were able to regulate the proliferation of other T cells. The ability of macrophages to regulate proliferation depends on activation by T cell-produced IFN-γ and autocrine TNF-α signaling in the myeloid cells via TNFR1. In the absence of TNFR1 signaling, relative T cell expansion in the retina is increased, indicating that regulatory myeloid cells may also act in vivo. However, TNFR1 signaling is also required for macrophages, but not T cells, to migrate into the target organ. Thus, in TNFR1 knock out mice, the amplification of autoimmunity is limited, leading to resistance to experimental autoimmune uveoretinitis induction.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Flow Cytometry and Cell Sortingmentioning

confidence: 99%

Section: Cell Culture and Assessment Of Cell Functionmentioning

confidence: 99%

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TNFR1-Dependent Regulation of Myeloid Cell Function in Experimental Autoimmune Uveoretinitis

Raveney¹,

Copland

Dick

et al. 2009

The Journal of Immunology

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“…Leukocytes were collected from the interface and where indicated cell numbers for leukocytes and/or T cell subsets per mouse were counted with an improved Neubauer counting chamber and via flow cytometry with reference to a cell number curve as previously described. 41 T cells were purified from splenocytes, draining lymph nodes and CNS infiltrates using a pan T cell MACS isolation kit with an AutoMACS separator according to manufacturer's instructions (Miltenyi Biotech, Bergisch Gladbach, Germany). Where required, naïve CD4 ϩ CD44 Ϫ CD25 Ϫ CD62L high T cells or memory CD4 ϩ CD44 ϩ CD25 Ϫ CD62L low T cells were further sorted using a fluorescence-activated cell sorter ARIA (BD Cytometry System, Franklin Lakes, NJ).…”

Section: Cell Isolation and Purificationmentioning

confidence: 99%

Synthetic Retinoid AM80 Inhibits Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis

Klemann

Raveney

Klemann

et al. 2009

The American Journal of Pathology

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Recent evidence suggests that interleukin-17-producing CD4؉ T cells (Th17 cells) are the dominant pathogenic cellular component in autoimmune inflammatory diseases, including multiple sclerosis. It has recently been demonstrated that all-trans retinoic acid can suppress Th17 differentiation and promote the generation of Foxp3 ؉ regulatory T cells via retinoic acid receptor signals. Here, we investigated the effects of AM80, a synthetic retinoid with enhanced biological properties to all-trans retinoic acid, on Th17 differentiation and function and evaluated its therapeutic potential in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. AM80 treatment was more effective than all-trans retinoic acid in inhibiting Th17 differentiation in vitro. Oral administration of AM80 was protective for the early development of EAE and the down-modulation of Th17 differentiation and effector functions in vivo. Moreover, AM80 inhibited interleukin-17 production by splenic memory T cells, in vitro-differentiated Th17 cells, and central nervous system-infiltrating effector T cells. Accordingly, AM80 was effective when administered therapeutically after the onset of EAE. Continuous AM80 treatment, however, was ineffective at inhibiting late EAE symptoms despite the maintained suppression of ROR␥t and interleukin-17 expression levels by central nervous system-infiltrating T cells. We reveal that continuous AM80 treatment also led to the suppression of interleukin-10 production by a distinct T cell subset that expressed both Foxp3 and ROR␥t. These findings suggest that retinoid signaling regulates both inflammatory Th17 cells and Th17-like regulatory cells. (Am J Pathol

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Fingolimod (FTY720) as an Acute Rescue Therapy for Intraocular Inflammatory Disease

Raveney¹,

Copland²,

Nicholson³

et al. 2008

Archives of Ophthalmology

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The B Subunit ofEscherichia coliHeat-Labile Enterotoxin Inhibits Th1 but Not Th17 Cell Responses in Established Experimental Autoimmune Uveoretinitis

Cited by 17 publications

References 51 publications

TNFR1-Dependent Regulation of Myeloid Cell Function in Experimental Autoimmune Uveoretinitis

TNFR1-Dependent Regulation of Myeloid Cell Function in Experimental Autoimmune Uveoretinitis

Synthetic Retinoid AM80 Inhibits Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis

Fingolimod (FTY720) as an Acute Rescue Therapy for Intraocular Inflammatory Disease

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