Differential expression of β2-integrins and cytokine production between γδ and αβ T cells in experimental autoimmune encephalomyelitis

Smith, Sherry S.; Barnum, Scott R.

doi:10.1189/jlb.0407263

Cited by 21 publications

(35 citation statements)

References 77 publications

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“…In agreement with our results, other authors have detected high levels of IL-17A in uninfected mice with ␥␦ T cells as the source of this cytokine (39,48). Those findings could partially explain the high concentration of IL-17A at day 0 in our experiment.…”

Section: Discussionsupporting

confidence: 83%

Nocardia brasiliensis Induces an Immunosuppressive Microenvironment That Favors Chronic Infection in BALB/c Mice

et al. 2012

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ABSTRACTNocardia brasiliensisis an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+Foxp3+regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whetherN. brasiliensismodulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship betweenN. brasiliensisimmunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P< 0.05) in footpad tissue and spleen. Treg subpopulations peaked at days 7 and 15 (P< 0.01) in the footpad and spleen, respectively. Transforming growth factor β1 (TGF-β1) and interleuki-10 (IL-10) are cytokines known for their immunosuppressive effects. During early and chronic infections, these cytokines were elevated with increased TGF-β1 levels from days 3 to 30 (P< 0.01) and sustained IL-10 expression throughout infection compared to uninfected mice. IL-6 production was increased at day 3 (P< 0.01), whereas gamma interferon (IFN-γ), IL-17A, and IL-23 levels were highest at day 15 postinfection (P< 0.01) when a decrease in the bacterial load (>1 log) was also observed (P< 0.05). After these changes, at 30 to 60 days postinfection, IFN-γ production was decreased, whereas the expression of anti-inflammatory cytokines and the bacterial load again increased (P< 0.05). The increment in Treg cells and the related cytokine profile correlated with reduced inflammation at day 15 (P< 0.05) in the footpad. We conclude thatN. brasiliensismodulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.

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Section: Discussionsupporting

confidence: 83%

Nocardia brasiliensis Induces an Immunosuppressive Microenvironment That Favors Chronic Infection in BALB/c Mice

et al. 2012

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“…It plays a critical role in complement-mediated phagocytosis and cellular trafficking, and in MScl, it ultimately contributes to the development of demyelinating disease (80,81). The differential regulation of ␤ 2 -integrins on certain T cell subsets during the acute course of EAE has been shown to modulate the kinetics of EAE development by influencing T cell migration patterns into peripheral and CNS tissues (82). We identified a 2.3 log 2 -fold decrease in Itgam expression within diseaseaffected PBMCs by spectral counting and label-free MRM analyses within disease-affected PBMCs.…”

Section: Molecular and Cellular Proteomics 133mentioning

confidence: 99%

Discovery of Novel Disease-specific and Membrane-associated Candidate Markers in a Mouse Model of Multiple Sclerosis

Dagley

Croft

Isserlin

et al. 2014

Molecular & Cellular Proteomics

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Multiple sclerosis is a chronic demyelinating disorder characterized by the infiltration of auto-reactive immune cells from the periphery into the central nervous system resulting in axonal injury and neuronal cell death. Experimental autoimmune encephalomyelitis represents the best characterized animal model as common clinical, histological, and immunological features are recapitulated. A label-free mass spectrometric proteomics approach was used to detect differences in protein abundance within specific fractions of disease-affected tissues including the soluble lysate derived from the spinal cord and membrane protein-enriched peripheral blood mononuclear cells. Tissues were harvested from actively induced experimental autoimmune encephalomyelitis mice and sham-induced ("vehicle" control) counterparts at the disease peak followed by subsequent analysis by nanoflow liquid chromatography tandem mass spectrometry. Relative protein quantitation was performed using both intensity-and fragmentation-based approaches. After statistical evaluation of the data, over 500 and 250 differentially abundant proteins were identified in the spinal cord and peripheral blood mononuclear cell data sets, respectively. More than half of these observations have not previously been linked to the disease. The biological significance of all candidate disease markers has been elucidated through rigorous literature searches, pathway analysis, and validation studies. Results from comprehensive targeted mass spectrometry analyses have confirmed the differential abundance of ϳ200 candidate markers (>twofold dysregulated expression) at a 70% success rate. This study is, to our knowledge, the first to examine the cell-surface proteome of peripheral blood mononuclear cells in experimental autoimmune encephalomyelitis. These data provide a unique mechanistic insight into the dynamics of peripheral immune cell infiltration into CNS-privileged sites at a molecular level and has identified several candidate markers, which represent promising targets for future multiple sclerosis therapies. The mass spectrometry proteomics data associated with this

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“…All mice were previously backcrossed to the C57BL/6 background for greater than eight generations and inbred C57BL/6 mice were used as controls. We induced EAE in wild type and C3aR/C5aR −/− mice as previously described [11]. Onset and progression of EAE symptoms was monitored daily using a standard clinical scale ranging from 0 to 6 as follows: 0, asymptomatic; 1, weak tail; 2, flaccid tail; 3, incomplete paralysis of one or two hind limbs; 4, complete hind limb paralysis; 5, moribund; 6, dead.…”

mentioning

confidence: 99%

“…For isolation of leukocytes and flow cytometry, mice were perfused and spinal cords were prepared and stained as previously described [11]. Cell preparations were incubated with anti-CD16/32 (FcR block, eBioscience) to prevent nonspecific staining.…”

mentioning

confidence: 99%

Deletion of both the C3a and C5a receptors fails to protect against experimental autoimmune encephalomyelitis

Ramos¹,

Wohler²,

Barnum³

2009

Neuroscience Letters

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Multiple sclerosis (MS) is an autoimmune disease in which inflammation, leukocyte infiltration, and ultimately, demyelination occur as a result of innate and adaptive immune-mediated mechanisms. The pathophysiological role of the complement system, a major component of innate immunity, in the development and progression of experimental autoimmune encephalomyelitis (EAE), the animal model for MS has been extensively examined. Previous studies from our lab have shown that the complement receptor for the anaphylatoxin C3a, but not for C5a plays an important role in EAE. Based on the important contributions of the complement anaphylatoxin receptors to other inflammatory conditions in the CNS, we reasoned that deletion of both receptors may reveal underlying interactions between them that are important to EAE pathology. We performed EAE in C3aR/C5aR double knockout mice (C3aR/C5aR −/− ) and observed delayed onset of disease but no attenuation of disease severity compared to wild type mice. Interestingly there was trend toward greater infiltration of CD4 + , but not CD8 + T cells, in C3aR/C5aR −/− mice with EAE, suggesting altered trafficking of these cells. Antigen-specific T cells isolated from C3aR/C5aR −/− mice during acute EAE produced elevated levels of TNF-α, but markedly reduced levels of IFN-γ and IL-12 compared to wild type mice. It remains unclear how the changes in these disease parameters contribute to the loss of the protective effect seen in C3aR −/− mice, however our data indicate a level of cross modulation between the C3aR and C5aR during EAE.

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Differential expression of β2-integrins and cytokine production between γδ and αβ T cells in experimental autoimmune encephalomyelitis

Cited by 21 publications

References 77 publications

Nocardia brasiliensis Induces an Immunosuppressive Microenvironment That Favors Chronic Infection in BALB/c Mice

Nocardia brasiliensis Induces an Immunosuppressive Microenvironment That Favors Chronic Infection in BALB/c Mice

Discovery of Novel Disease-specific and Membrane-associated Candidate Markers in a Mouse Model of Multiple Sclerosis

Deletion of both the C3a and C5a receptors fails to protect against experimental autoimmune encephalomyelitis

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