Experimental Autoimmune Encephalomyelitis in the Mouse

Miller, Stephen D.; Karpus, William J.

doi:10.1002/0471142735.im1501s77

Cited by 249 publications

(176 citation statements)

References 66 publications

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“…EAE is an inflammatory autoimmune disease of the CNS that serves as a model for MS (1)(2)(3)(4). In EAE and MS, CD4 + effector T cells, proliferating in response to myelin antigens, are likely to promote the development and progression of each disease (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

Zohar¹,

Wildbaum²,

Novak³

et al. 2014

J. Clin. Invest.

141

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A single G protein-coupled receptor (GPCR) can activate multiple signaling cascades based on the binding of different ligands. The biological relevance of this feature in immune regulation has not been evaluated. The chemokine-binding GPCR CXCR3 is preferentially expressed on CD4+ T cells, and canonically binds 3 structurally related chemokines: CXCL9, CXCL10, and CXCL11. Here we have shown that CXCL10/CXCR3 interactions drive effector Th1 polarization via STAT1, STAT4, and STAT5 phosphorylation, while CXCL11/ CXCR3 binding induces an immunotolerizing state that is characterized by IL-10 hi (Tr1) and IL-4 hi (Th2) cells, mediated via p70 kinase/mTOR in STAT3-and STAT6-dependent pathways. CXCL11 binds CXCR3 with a higher affinity than CXCL10, suggesting that CXCL11 has the potential to restrain inflammatory autoimmunity. We generated a CXCL11-Ig fusion molecule and evaluated its use in the EAE model of inflammatory autoimmune disease. Administration of CXCL11-Ig during the first episode of relapsing EAE in SJL/J mice not only led to rapid remission, but also prevented subsequent relapse. Using GFP-expressing effector CD4 + T cells, we observed that successful therapy was associated with reduced accumulation of these cells at the autoimmune site. Finally, we showed that very low doses of CXCL11 rapidly suppress signs of EAE in C57BL/6 mice lacking functional CXCL11.

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Section: Introductionmentioning

confidence: 99%

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

Zohar¹,

Wildbaum²,

Novak³

et al. 2014

J. Clin. Invest.

141

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“…T-cells generated through this immunization are able to pass through the blood-brain barrier (BBB) and propagate an influx of monocytes into the CNS. Subsequent activation of resident microglia and perhaps CNS cells, such as astrocytes lead to the demyelination of axons and axonal loss (Miller & Karpus 2007).…”

Section: Introductionmentioning

confidence: 99%

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Haghmorad

Salehipour

Nosratabadi

et al. 2016

Journal of Immunotoxicology

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Estrogen is a neuro-protective hormone in various central nervous system (CNS) disorders. The present study evaluated the role of estrogen during experimental autoimmune encephalomyelitis (EAE) at doses selected to mimic any suppressive potential from the hormone during pregnancy. Here, mice were ovariectomized and then 2 weeks later treated with MOG antigen to induce EAE. Concurrently, mice then received (subcutaneously) an implanted pellet to deliver varying estrogen amounts over a 21-day period. Clinical scores and other parameters were monitored daily for the 21 days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T-cell differentiation was evaluated via flow cytometry. The results demonstrated that estrogen inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. High and medium dose of estrogen increased T H 2 and T reg cell production of interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-b, but concurrently resulted in a significant reduction in production of interferon (IFN)-c, IL-17, and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of T H 1 and T H 17 cells, as well as significant increase in percentages of T reg and T H 2 cells in the spleen and lymph nodes. Real-time PCR results indicated that high-and medium-dose estrogen treatments reduced T-bet and ROR-ct factor expression, but enhanced Foxp3 and GATA3 expression. Collectively, these results demonstrated that a medium dose of estrogen -similar to a pregnancy level of estrogen -could potentially reduce the incidence and severity of autoimmune EAE and possibly other autoimmune pathologies.ARTICLE HISTORY

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“…To understand the CNS pathogenesis during RF, we infected C57BL/6 mice with DAH, a clinical isolate of B. hermsii, and visually monitored them daily for signs of neurologic disease. Surprisingly, a high percentage of B. hermsii-infected mice exhibited symptoms that are similar to the neurologic disease manifestations described for classical EAE, such as tail/hind limb weakness or paralysis (19). In addition, a minor fraction of (∼5%) of infected mice showed vestibular dysfunction characterized by uncontrolled axial rotation when lifted by tail (not shown).…”

Section: B Hermsii Infection Causes Distinct Neurologic Manifestatiomentioning

confidence: 68%

“…To quantify the neurologic manifestations associated with B. hermsii infection, we evaluated infected mice using a grading system described for studying EAE (19). During the primary bacteremic episode (day 2-4 postinfection [data not shown]) no discernable signs of neurologic manifestations were detected.…”

Section: B Hermsii Infection Causes Distinct Neurologic Manifestatiomentioning

confidence: 99%

Induction of Distinct Neurologic Disease Manifestations during Relapsing Fever Requires T Lymphocytes

Liu¹,

Fitzgerald

Gran

et al. 2010

The Journal of Immunology

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Relapsing fever borreliosis is a multisystemic infection characterized primarily by bacteremia but can extend to the CNS. The incidence of CNS disease manifestations in humans depends on the infecting relapsing fever Borrelia species. In the murine model of Borrelia hermsii infection we found high incidence of distinct signs of CNS disease that ranged from a flaccid tail to complete paralysis of hind limbs. Infiltration of large number of T cells into the spinal cord of B. hermsii-infected mice and the upregulation of MHC class II and CD80 on infiltrating macrophages and on microglial cells suggested a role for T cell and Ag-presenting cell interactions in this pathogenesis. Indeed, B. hermsii infection did not induce CNS disease manifestations in T cell-deficient mice (TCR-β × δ−/−), although it resulted in bacteremia comparable to wild-type (Wt) level. Moreover, the infiltration of immune cells into the spinal cord of TCR-β × δ−/− mice was reduced and the resident microglial cells were not activated. Histopathological analysis of lumbar sections of the spinal cord confirmed severe inflammation in Wt but not in TCR-β × δ−/− mice. Induction of CNS disease was dependent on the B. hermsii strain as well as on the ability of the host to control bacteremia. Mice that are impaired in controlling B. hermsii, such as CD14−/− mice, exhibited more severe CNS disease than Wt mice. This study demonstrates that distinct neurologic disease manifestations develop during relapsing fever and that T cells play a critical role in the induction of neuropathogenesis.

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Experimental Autoimmune Encephalomyelitis in the Mouse

Cited by 249 publications

References 66 publications

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Induction of Distinct Neurologic Disease Manifestations during Relapsing Fever Requires T Lymphocytes

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