Role of Th1 and Th2 cells in autoimmune demyelinating disease

Nagelkerken, Lex

doi:10.1590/s0100-879x1998000100007

Cited by 28 publications

(17 citation statements)

References 55 publications

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“…Recent studies have indicated that Th17 cells and IFN-γ-secreting Th1 cells play an important role in the clinical pathogenesis in EAE/MS disease (Komiyama et al, 2006; Nagelkerken, 1998; Segal, 2003; Skarica et al, 2009; Yura et al, 2001). In addition, proinflammatory cytokines such as TNFα and IL-6 are also considered important for induction and pathogenesis involving inflammation and neuroglial damage (Penkowa and Hidalgo, 2001; Villarroya et al, 1997; Wiemann et al, 1998).…”

Section: Resultsmentioning

confidence: 99%

Immune modulation by chondroitin sulfate and its degraded disaccharide product in the development of an experimental model of multiple sclerosis

Zhou

Nagarkatti

Yin

et al. 2010

Journal of Neuroimmunology

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Clinical symptoms in MOG-induced EAE mice significantly exacerbated following hondroitin sulfate A (CS-A) injection, whereas administration of a degraded product, CSPG-DS, caused dramatic inhibition of EAE development. Also, administration of CSPG-DS but not CS-A, after the onset of clinical symptoms of EAE, was able to suppress the disease. Further studies demonstrated that CS-A up-regulated STAT4 expression and thus, induced IFN-γ production and Th1 CD4 T cell differenttiation. CS-A also up-regulated STAT3 and IL-23 expression and thus increased IL-17 producing T cells. CSPG-DS treatment both in vivo and in vitro decreased TNFα production from splenocytes. In vitro and in vivo studies indicated that CSPG-DS treatment in EAE mice significantly blocked migration of lymphocytes, whereas CS-A treatment increased lymphocyte infiltration in the brain.

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Section: Resultsmentioning

confidence: 99%

Immune modulation by chondroitin sulfate and its degraded disaccharide product in the development of an experimental model of multiple sclerosis

Zhou

Nagarkatti

Yin

et al. 2010

Journal of Neuroimmunology

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“…The rapid activation of both a TH1 and TH2 response in fetal brains exposed to intrauterine LPS observed in this study suggest that these responses play an early and crucial role in preterm brain injury. Prolonged activation of a TH1 response is implicated in white matter damage in active inflammatory states within the CNS (31). In contrast, TH2 cytokines or agents that augment a TH2 response have been demonstrated to ameliorate disease progression (32,33).…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Early Signal Transduction Pathways Leading to Fetal Brain Injury in Preterm Birth

2006

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Adverse neurologic outcome, including cerebral palsy, is a significant contributor to long-term morbidity in preterm neonates. However, the mechanisms leading to brain injury in the setting of a preterm birth are poorly understood. In the last decade, there has been a growing body of evidence correlating infection or inflammation with preterm birth. The presence of intrauterine inflammation significantly increases the risk for adverse neurologic outcome in the neonate. These studies were performed to elucidate the early signal transduction pathways activated in the fetal brain that may result in long-term neurologic injury. Using our mouse model of localized intrauterine inflammation, the activation of TH1/TH2 pathways in the placenta, fetus corpus, fetal liver, and fetal brain was investigated. Additional studies determined whether activation of TH1/TH2 pathways could promote cell death and alter glial development. Real-time PCR studies demonstrated that a robust TH1/TH2 response occurs rapidly in the fetal brain after exposure to intrauterine inflammation. The cytokine response in the fetus and placenta was not significantly correlated with the response in the fetal brain. Along with an immune response, cell death pathways were activated early in the fetal brain in response to intrauterine LPS. Implicating TH1/TH2 and cell death pathways in permanent brain injury are our findings of an increase in GFAP mRNA and protein as well as a loss of pro-oligodendrocytes. With increased understanding of the mechanisms by which inflammation promotes brain injury in the preterm neonate, identification of potential targets to limit adverse neonatal outcomes becomes possible. (Pediatr Res 59: 50-55, 2006)

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“…Given the key role of STAT1 in the development of T H 1 cells, which are implicated in the onset of EAE, compared with T H 2 cells that promote recovery from the disease, the inhibition of IFNγ-dependent STAT1 activation could be used as a means to normalize the T H 1–T H 2 balance and promote recovery from the EAE phenotype 145,146 .…”

Section: Inhibitors Of Stat1 and Stat4mentioning

confidence: 99%

Therapeutic modulators of STAT signalling for human diseases

Miklóssy

Hilliard

Turkson

2013

Nat Rev Drug Discov

354

334

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The signal transducer and activator of transcription (STAT) proteins have important roles in biological processes. The abnormal activation of STAT signalling pathways is also implicated in many human diseases, including cancer, autoimmune diseases, rheumatoid arthritis, asthma and diabetes. Over a decade has passed since the first inhibitor of a STAT protein was reported and efforts to discover modulators of STAT signalling as therapeutics continue. This Review discusses the outcomes of the ongoing drug discovery research endeavours against STAT proteins, provides perspectives on new directions for accelerating the discovery of drug candidates, and highlights the noteworthy candidate therapeutics that have progressed to clinical trials.

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Role of Th1 and Th2 cells in autoimmune demyelinating disease

Cited by 28 publications

References 55 publications

Immune modulation by chondroitin sulfate and its degraded disaccharide product in the development of an experimental model of multiple sclerosis

Immune modulation by chondroitin sulfate and its degraded disaccharide product in the development of an experimental model of multiple sclerosis

Elucidating the Early Signal Transduction Pathways Leading to Fetal Brain Injury in Preterm Birth

Therapeutic modulators of STAT signalling for human diseases

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