IFN-γ deficiency exacerbates experimental autoimmune neuritis in mice despite a mitigated systemic Th1 immune response

Zhang, Hong‐Liang; Azimullah, Sheikh; Zheng, Xiangyu; Wang, Xiaoke; Amir, Naheed; Mensah-Brown, Eric; Shamsi, Mariam Al; Shahin, Allen; Zhu, Jie; Adem, Abdu

doi:10.1016/j.jneuroim.2012.02.011

Cited by 29 publications

(27 citation statements)

References 188 publications

(184 reference statements)

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“…Whereas, some changes in experimental autoimmune neuritis (EAN), an animal model of human GBS could not be explained by this opinion perfectly. Zhang et al found that IFN- γ knockout mice were also susceptible to EAN [23], this indicated other factors and mechanisms are involved. Moreover, IL-17A positive cells in cauda equina (CE) infiltrating cells, and the levels of IL-17A in sera were increased in IFN- γ knockout mice [23].…”

Section: Discussionmentioning

confidence: 99%

“…Zhang et al found that IFN- γ knockout mice were also susceptible to EAN [23], this indicated other factors and mechanisms are involved. Moreover, IL-17A positive cells in cauda equina (CE) infiltrating cells, and the levels of IL-17A in sera were increased in IFN- γ knockout mice [23]. IL-17 was found in sciatic nerves of EAN, and the accumulation of IL-17 was correlated with the severity of neurological signs [24], which suggested a pathological contribution of IL-17 to the development of EAN.…”

Section: Discussionmentioning

confidence: 99%

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IL-17 and IL-22 in Cerebrospinal Fluid and Plasma Are Elevated in Guillain-Barré Syndrome

et al. 2012

Mediators of Inflammation

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Guillain-Barré syndrome (GBS) is an acute autoimmune-mediated inflammatory demyelinating disease that causes rapidly progressing paralysis and occasionally respiratory failure. We hypothesized that interleukin (IL)-17 and IL-22 are elevated in GBS and participate in the autoimmune inflammatory response of GBS. We used sandwich enzyme-linked immunosorbent assay (ELISA) to measure the IL-17 and IL-22 levels in the CSF, and plasma from 22 GBS patients at the acute phase and 18 healthy controls (HC). The results show that CSF and plasma levels of IL-17 and IL-22 are elevated in GBS patients compared with HC. IL-17 and IL-22 levels in CSF, respectively, are correlated with GBS disability scale scores (GDSs). Meanwhile, IL-17 and IL-22 levels in CSF, IL-22 in CSF, and plasma of GBS patients have positive correlation, respectively. The increased levels of IL-17 and IL-22 in CSF may be explained by the disruption of blood-brain barrier (BBB) and peripheral nervous system (PNS) local inflammation in GBS. Meanwhile, the elevated levels of these two cytokines in plasma suggest the activation of Th17 and Th22 cells in the systemic immune response of GBS. Our data provide preliminary evidence that GBS is associated with high levels of IL-17 and IL-22 in CSF and plasma. These cytokines display pathogenic potential and may serve as useful biomarkers for GBS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

IL-17 and IL-22 in Cerebrospinal Fluid and Plasma Are Elevated in Guillain-Barré Syndrome

et al. 2012

Mediators of Inflammation

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“…The pathogenesis of GBS remains still enigmatic, but it is largely accepted that both cellular and humoral immune responses are involved in the pathogenesis of GBS [5, 6]. AIDP and its animal model experimental autoimmune neuritis (EAN) have hitherto been classified to Th1 cells-mediated disorders [7–9]. Th1 cells, a subset of CD4 + T (T helper) cells, are dominant in the inflamed nerves at the acute phase of GBS [8], which could produce IFN- γ as a major pathogenic cytokine in GBS, because increased IFN- γ was seen in the serum of GBS patients at acute phase [10], and higher immunoreactivity for IFN- γ was showed in sural nerves biopsies of GBS patients [11].…”

Section: Introductionmentioning

confidence: 99%

“…Th17 cell frequency was higher in the cerebrospinal fluid of the patients with relapsing-remitting multiple sclerosis (MS) during the relapse phase [22]. Recently, we reported an aggravated clinical course of EAN in IFN- γ deficient mice, concomitant with an upregulated level of Th17 cells, indicating a pathogenic role of Th17 in EAN [9]. EAN was attenuated by atorvastatin treatment, a lipid lowering drug with anti-inflammatory properties, and the level of IL-17A was decreased in parallel [23].…”

Section: Introductionmentioning

confidence: 99%

Circulating Th17, Th22, and Th1 Cells Are Elevated in the Guillain-Barré Syndrome and Downregulated by IVIg Treatments

Jin

Zhang

et al. 2014

Mediators of Inflammation

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The Guillain-Barré syndrome (GBS) is considered a T helper 1 (Th1) cells-mediated acute inflammatory peripheral neuropathy. However, some changes in GBS could not be explained completely by Th1 cells pathogenic role. Recently, Th17 cells have been identified and can mediate tissue inflammation and autoimmune response. Therefore, a study on the role of Th17 and Th22 cells and their cytokines in GBS is necessary for exploring the pathogenesis of GBS. Here, we detected the frequency of Th1, Th17, and Th22 cells by using 4-color flow cytometry and we detected the plasma levels of IL-17 and IL-22 by ELISA in GBS patients, relapsing-remitting multiple sclerosis patients at the acute phase of relapse, viral encephalitis or meningitis patients and healthy controls. Our data showed that the frequency of circulating Th1, Th17, and Th22 cells was significantly increased in GBS patients. The plasma levels of IL-17 and IL-22 in GBS and relapsing-remitting multiple sclerosis at the acute phase of relapse were also markedly elevated. Enhanced circulating Th22 cells were correlated with GBS severity. Intravenous immunoglobulin therapy downregulated Th17, and Th22 cells and the plasma levels of IL-17 and IL-22 in GBS patients. Th17 and Th22 cells may be involved in the pathogenesis of GBS, and intravenous immunoglobulin mediates therapeutic effects by downregulating these cells and their cytokines.

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“…IFN-g is implicated in B cell activation and class switching, DC maturation, and also in suppressing Th17 differentiation and bone resorption [13]. The reduced IFN-g expression due to decreased NK and NKT cells allows the uncontrolled proliferation of Th17 cells that are responsible for disease pathogenesis of a number of autoimmune disorders [61]. Another possible explanation of the present results is related to the ability of NK cells to lyse autologous antigen-presenting cells such as DC, thus limiting the magnitude of an immune response [62].…”

Section: Discussionmentioning

confidence: 99%

Bi(o)communications among peripheral blood fractions: A focus on NK and NKT cell biology in rheumatoid arthritis

2012

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Rheumatoid Arthritis (RA) is an autoimmune disease with unknown pathophysiology involving many interwoven signalling cascades. ROS, NK and NKT cells might be crucial in the disease severity of RA of which the role of NK and NKT cells are controversial in literature. However, the role of oxidative stress, its impact on NK and NKT cell immunobiology and disease activity (DAS28) is largely unknown. Therefore, we studied the role of oxidative stress and NK cell subsets in the pathogenesis of RA. The state of oxidative stress in various peripheral blood fractions, percentage NK and NKT cell expression, their altered apoptotic signaling pathways involving mitochondrial membrane potential, FAS associated death domain (FADD) mediated pathways and DNA damage were analyzed. Results indicated a state of profound oxidative stress in the peripheral blood of RA patients where percentage of NK and NKT cell subsets diminished while ROS levels increased. The depolarized mitochondrial membrane potential, FAS, FASL and active caspase-3 positive NK and NKT cell subsets were considerably elevated in patients. The DNA damage, assessed as percentage of DNA in comet tail, was significantly elevated. Findings of the present work indicate increased apoptosis of peripheral NK and NKT cells in the diseased condition. PBMC and RBC are the major sites of enhanced oxidative stress. The state of oxidative stress and altered immunobiology of NK and NKT cells strongly correlated with Disease activity score. The present study strongly supports the protective role of NK cell subsets in the pathogenesis of RA.

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IFN-γ deficiency exacerbates experimental autoimmune neuritis in mice despite a mitigated systemic Th1 immune response

Cited by 29 publications

References 188 publications

IL-17 and IL-22 in Cerebrospinal Fluid and Plasma Are Elevated in Guillain-Barré Syndrome

IL-17 and IL-22 in Cerebrospinal Fluid and Plasma Are Elevated in Guillain-Barré Syndrome

Circulating Th17, Th22, and Th1 Cells Are Elevated in the Guillain-Barré Syndrome and Downregulated by IVIg Treatments

Bi(o)communications among peripheral blood fractions: A focus on NK and NKT cell biology in rheumatoid arthritis

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