| 1. |
- Bäcklund, Johan, et al.
(författare)
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Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.
- 2002
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Ingår i: European Journal of Immunology. - 1521-4141. ; 32:12, s. 3776-3784
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Tidskriftsartikel (refereegranskat)abstract
- Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the galactosylated peptide (galactoseat position 264) was superior in protecting mice from CIA. Protection was accompanied by a reduced antibody response to CII and by an impaired T cell response to the glycopeptide. To investigate the importance of glycopeptide recognition in an autologous CIA model, we treated MMC-transgenic mice, which express the heterologous CII epitope with a glutamic acid in position 266 in cartilage, with CII-peptides. Again, a strong vaccination potential of the glycopeptide was seen. Hence CII-glycopeptides may be the optimal choice of vaccination target in RA, since humans share the same epitope as the MMC mouse
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| 2. |
- Ejlerskov, Patrick, et al.
(författare)
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Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia.
- 2015
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 163:2, s. 324-339
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative diseases have been linked to inflammation, but whether altered immunomodulation plays a causative role in neurodegeneration is not clear. We show that lack of cytokine interferon-β (IFN-β) signaling causes spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying α-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-β signaling caused defects in neuronal autophagy prior to α-synucleinopathy, which was associated with accumulation of senescent mitochondria. Recombinant IFN-β promoted neurite growth and branching, autophagy flux, and α-synuclein degradation in neurons. In addition, lentiviral IFN-β overexpression prevented dopaminergic neuron loss in a familial Parkinson's disease model. These results indicate a protective role for IFN-β in neuronal homeostasis and validate Ifnb mutant mice as a model for sporadic Lewy body and Parkinson's disease dementia.
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| 3. |
- Inacio, Ana, et al.
(författare)
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Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia.
- 2015
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-β signaling in stroke are unclear.
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| 4. |
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| 5. |
- Liu, Yawei, et al.
(författare)
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Suppression of EAE by oral tolerance is independent of endogenous IFN-beta whereas treatment with recombinant IFN-beta ameliorates EAE.
- 2010
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Ingår i: Immunology and Cell Biology. - : Wiley. - 1440-1711 .- 0818-9641. ; 88, s. 468-476
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Tidskriftsartikel (refereegranskat)abstract
- IFN-beta is anticipated to have an important function in mucosal tolerance, as it is one of the major cytokines produced by plasmacytoid dendritic cells, and has recently been suggested as central to the maintenance of mucosal homeostasis. Here, we have investigated whether oral tolerance is dependent on endogenous IFN-beta by feeding low-dose self-antigen myelin basic protein to IFN-beta(-/-) mice with subsequent induction of experimental autoimmune encephalomyelitis (EAE). Our study shows that oral tolerance was readily induced in IFN-beta(-/-) mice compared with their wild-type littermates (IFN-beta(+/+)). The non-self-antigen ovalbumin induced oral tolerance in both groups. These data indicate that endogenous IFN-beta is not required for induction of oral tolerance, whereas delivery of recombinant IFN-beta results in significant reduction in clinical score of EAE. Oral tolerance induction was associated with lower production of antigen-specific IFN-gamma, no shift toward antigen-specific Th2, Th17 or TGF-beta response was observed. Oral tolerance in IFN-beta(-/-) mice was also associated with the induction of regulatory and memory T cells in the mucosal-associated immune organs, however this was not a prerequisite for establishment of oral tolerance.Immunology and Cell Biology advance online publication, 12 January 2010; doi:10.1038/icb.2009.111.
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| 6. |
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| 7. |
- Matheu, Victor, et al.
(författare)
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Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.
- 2005
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 6:1, s. 25-25
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known. OBJECTIVE: Here, we aimed to elucidate the role of IFN-beta in the anti-allergic effect of CpG motifs. METHODS: We assessed the immune response in OVA-primed/OVA-challenged IFN-beta knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs. RESULTS: Vaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-beta-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-beta-/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-beta-/- mice. The ratio of IFN-gamma/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-beta-/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-gamma, IL-2 and also IL-12 were significantly lower in IFN-beta-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-beta-/- mice. CONCLUSION: Our results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-beta, while IFN-beta is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination.
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| 8. |
- Matheu, Victor, et al.
(författare)
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Similar response in male and female B10.RIII mice in a murine model of allergic airway inflammation.
- 2010
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Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 59:4, s. 263-269
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several reports have been published on the gender differences associated with allergies in mice. GOAL: In the present study we investigate the influence of gender on allergy response using a strain of mice, B10.RIII, which is commonly used in the collagen-induced arthritis murine model. METHODS: Both male and female B10.RIII young mice were immunized with OVA and challenged four times with OVA intranasally. Samples were taken 24 h after the last challenge, and eosinophils in bronchoalveolar lavage (BAL) and parenchyma, Th-2 cytokines in BAL, total and antigen-specific IgE in sera, and antigen-specific T-cell proliferation were measured. RESULTS: Immunization in both male and female B10.RIII mice with OVA elicited a classical Th2-type response. Results showed no significant differences among male and female mice. Also a high eosinophilia in BAL fluid and parenchyma was produced in both genders without any significant differences. However, the deviation of both parameters was higher in young males compared to young females. CONCLUSIONS: Gender differences, classically associated with some strains of mice, are not reproducible in B10.RIII mice. Gender differences in murine models of allergic airway inflammation are probably strain-dependent.
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| 9. |
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| 10. |
- Teige, Anna, et al.
(författare)
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CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis.
- 2004
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Ingår i: Journal of Immunology. - 1550-6606. ; 172:1, s. 186-194
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Tidskriftsartikel (refereegranskat)abstract
- The existence of T cells restricted for the MHC I-like molecule CD1 is well established, but the function of these cells is still obscure; one implication is that CD1-dependent T cells regulate autoimmunity. In this study, we investigate their role in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, using CD1-deficient mice on a C57BL/6 background. We show that CD1-/- mice develop a clinically more severe and chronic EAE compared with CD1+/+ C57BL/6 mice, which was histopathologically confirmed with increased demyelination and CNS infiltration in CD1-/- mice. Autoantigen rechallenge in vitro revealed similar T cell proliferation in CD1+/+ and CD1-/- mice but an amplified cytokine response in CD1-/- mice as measured by both the Th1 cytokine IFN-{gamma} and the Th2 cytokine IL-4. Investigation of cytokine production at the site of inflammation showed a CNS influx of TGF-{beta}1-producing cells early in the disease in CD1+/+ mice, which was absent in the CD1-/- mice. Passive transfer of EAE using an autoreactive T cell line induced equivalent disease in both groups, which suggested additional requirements for activation of the CD1-dependent regulatory pathway(s). When immunized with CFA before T cell transfer, the CD1-/- mice again developed an augmented EAE compared with CD1+/+ mice. We suggest that CD1 exerts its function during CFA-mediated activation, regulating development of EAE both through enhancing TGF-{beta}1 production and through limiting autoreactive T cell activation, but not necessarily via effects on the Th1/Th2 balance.
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