| 1. |
- Börjesson, Andreas, et al.
(författare)
-
beta-cell specific overexpression of suppressor of cytokine signalling-3 does not protect against multiple low dose streptozotocin induced type 1 diabetes in mice
- 2011
-
Ingår i: Immunology Letters. - : Elsevier BV. - 0165-2478 .- 1879-0542. ; 136:1, s. 74-79
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the impact of beta-cell specific overexpression of suppressor of cytokine signalling-3 (SOCS-3) on the development of multiple low dose streptozotocin (MLDSTZ) induced Type 1 diabetes and the possible mechanisms involved. MLDSTZ treatment was administered to RIP-SOCS-3 transgenic and wild-type (wt) mice and progression of hyperglycemia monitored. Isolated islets from both strains were exposed to human IL-1 beta (25 U/ml) or a combination of human IL-1 beta (25 U/ml) and murine IFN-gamma (1000 U/ml) for 24h or 48h and we investigated the expression of IL-1 receptor antagonist (IL-1Ra) mRNA in islet cells and secretion of IL-1Ra into culture medium. MLDSTZ treatment caused gradual hyperglycemia both in the wt mice and in the transgenic mice with the latter tending to be more sensitive. In vitro experiments on wt and transgenic islets did not reveal any differences in sensitivity to damaging effects of STZ. Exposure of wt islets to 1L-1 beta or IL-1 beta + IFN-gamma seemed to lead to a failing IL-1Ra response from SOCS-3 transgenic islets. It could be that an increased expression of a possible protective molecule against beta-cell destruction may lead to a dampered response of another putative protective molecule. This may have counteracted a protective effect against MLDSTZ in SOCS-3 transgenic mice.
|
|
| 2. |
- Gasperov, Nina Milutin, et al.
(författare)
-
Epigenetic activation of immune genes in cervical cancer
- 2014
-
Ingår i: Immunology Letters. - : Elsevier. - 0165-2478 .- 1879-0542. ; 162:2, s. 256-257
-
Tidskriftsartikel (refereegranskat)abstract
- Immune system provides us protection from infectious pathogens and tumors formation during lifetime. Cervical cancer (CC), and its cause, human papillomavirus (HPV) are both challenges for the immune system. We present here evidence of epigenetic activation of immune system genes in CC. Illumina Infinium Human Methylation 450 K BeadChip identified genes, which were all significantly hypomethylated in CC tissue versus normal tissue. The GeneMANIA computer program identified a tight network between those genes. The most strongly correlated genes based on their function are immune effectors' process (AIM2, BST2, BTN3A3, and IL12RB1) and response to virus related genes (AIM2, BST2, and IL12RB1). Thus, activation of those genes through demethylation is probably triggered by HPV oncogenes. In conclusion, the immune system of women who do not develop CC is probably activated earlier through DNA demethylation.
|
|
| 3. |
|
|
| 4. |
- Ludvigsson, Johnny
(författare)
-
Combination therapy for preservation of beta cell function in Type 1 diabetes: New attitudes and strategies are needed!
- 2014
-
Ingår i: Immunology Letters. - : Elsevier. - 0165-2478 .- 1879-0542. ; 159:1-2, s. 30-35
-
Forskningsöversikt (refereegranskat)abstract
- In several diseases where the immune system plays an important role there has been a tremendous progress in treatment efficacy during the last decades. Based on necessary basic science these improvements are results of rapid, numerous and open-minded clinical trials where pieces of positive results step by step have been added into treatment schemes. Treatment of Type 1 diabetes has certainly improved but too slowly. It has been difficult to convince the scientific community of opinions which among non-professionals have been regarded as common sense such as the value of normal blood glucose and preservation of insulin secretion. Lack of motivation to participate in clinical trials has slowed down progress, as well as too narrow views on both pathogenesis of Type 1 diabetes and how studies should be designed to test therapeutic interventions. Studies in experimental animals can create and support hypothesis for human conditions but must not delay clinical trials too long. There is already evidence enough for intervention trials where immune suppression is combined with antigen treatment, beta cell protection, anti-inflammatory treatment, and efforts to stimulate beta cell regeneration. Regimens should be elaborated and first tried in those groups of patients where response can be expected to be best, and thereafter adjusted to increase efficacy step-wise, and in broader patient categories.
|
|
| 5. |
- Magnusson, Sofia E, et al.
(författare)
-
Dysregulated Fc receptor function in active rheumatoid arthritis
- 2014
-
Ingår i: Immunology Letters. - : Elsevier BV. - 0165-2478 .- 1879-0542. ; 162:1 Pt A, s. 200-206
-
Tidskriftsartikel (refereegranskat)abstract
- Given the critical role of Fc gamma receptors (FcgammaR) as primary targets for autoantibody-mediated effects an important issue is how the FcgammaR pathway is affected in autoimmune disorders. Here we investigated the FcgammaR function in monocytes from rheumatoid arthritis (RA) patients in relation to immunoglobulin levels and disease activity. Peripheral blood was obtained from 30 RA patients with clinical acute joint synovitis (active RA), 28 RA patients with no clinical signs of acute joint synovitis (non-active RA) and 34 healthy controls. Prior the functional studies the monocytes were characterized of their FcgammaRI (CD64), II (CD32), IIb (CD32b) and III (CD16) expression as well as their cell surface bound IgG. The monocytic FcgammaR function was assessed by binding of human IgG1 and IgG3 immune complexes (IC) and TNF secretion in vitro. IgG anti-citrullinated peptide antibodies (ACPA) were analyzed in the plasma. We found that monocytes from active RA patients had increased levels of FcgammaRI, II and cell surface IgG concurrently with impaired FcgammaR function. This was evident by reduced IgG1-IC binding and decreased TNF secretion in response to IgG3-IC. In contrast, monocytes from non-active RA patients displayed a normal FcgammaR function and had increased FcgammaRIIb expression together with elevated FcgammaRI, II and cell surface IgG. The ACPA levels did not differ in active and non-active RA patients but correlated with the monocytic FcgammaRIII expression in the patients. In conclusion, active RA patients display a dysregulated FcgammaR function that may represent a novel phenotypic and likely pathogenetic marker for active RA. A disease and FcgammaR function controlling effect is suggested by the increased inhibitory FcgammaRIIb in non-active RA.
|
|
| 6. |
|
|
| 7. |
- Skoglund, Caroline, et al.
(författare)
-
C1q regulates collagen-dependent production of reactive oxygen species, aggregation and levels of soluble P-selectin in whole blood
- 2012
-
Ingår i: Immunology Letters. - Amsterdam, Netherlands : Elsevier. - 0165-2478 .- 1879-0542. ; 142:1-2, s. 28-33
-
Tidskriftsartikel (refereegranskat)abstract
- Blood platelets express several receptors involved in immunity (e.g. complement-, toll-like- and Fc gamma-receptors) and release inflammatory mediators. Furthermore, formation of platelet-leukocyte aggregates has an important role during inflammatory conditions such as coronary artery disease. Thus, apart from their well-known role in haemostasis, platelets are today also recognized as cells with immunomodulatory properties. We have previously reported regulatory effects of complement protein 1q (C1q) on platelet activation in experimental setups using isolated cells. In the present study we have proceeded by investigating effects of C1q on collagen-induced aggregation, production of reactive oxygen species (ROS), formation of platelet-leukocyte aggregates and levels of soluble P-selectin in whole blood. Impedance measurements showed that C1q inhibited collagen-induced aggregation whereas it potentiated the collagen-provoked production of ROS in a luminol-dependent chemiluminescence assay. The effects of C1q on aggregation and ROS-production were dependent upon platelets, as they were no longer observed in presence of the platelet (GpIIb/IIIa) inhibitor Reopro. Furthermore, the levels of soluble P-selectin were found to be lowered upon treatment with C1q prior to addition of collagen. There was also a trend towards a decreased formation of large platelet-leukocyte aggregates in collagen-stimulated whole blood following C1q treatment. In conclusion, our data indicate that C1q could have a role in regulating platelet activation and associated leukocyte recruitment during vessel wall injury. This has implications for inflammatory disorders such as coronary artery disease.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Shao, Wei, et al.
(författare)
-
Combination of monoclonal antibodies with DST inhibits accelerated rejection mediated by memory T cells to induce long-lived heart allograft acceptance in mice
- 2011
-
Ingår i: Immunology Letters. - : Elsevier BV. - 0165-2478. ; 138:2, s. 122-128
-
Tidskriftsartikel (refereegranskat)abstract
- Donor-reactive memory T cells mediated accelerated rejection is known as a barrier to the survival of transplanted organs. We investigated the combination of different monoclonal antibodies (mAbs) and donor-specific transfusion (DST) in memory T cells-based adoptive mice model. In the presence of donor reactive memory T cells, the mean survival time (MST) of grafts in the anti-CD40L/LFA-1/DST group was 49.8 d. Adding anti-CD44/CD70 mAbs to anti-CD40L/LFA-1/DST treatment. The MST was more than 100 d (MST > 100 d). Compared with anti-CD40L/LFA-1/DST group, anti-CD40L/LFA-1/CD44/CD70/DST group notably reduced the expansion of memory T cells, enhanced the proportion of CD4(+)Foxp3(+) regulatory T cells (Tregs) and suppressed donor-specific responses. Our data suggest that anti-CD40L/LFA--1/CD44/CD70 mAbs and DST can synergistically inhibit accelerated rejection mediated by memory T cells to induce long-lived heart allograft acceptance in mice. (C) 2011 Elsevier B.V. All rights reserved.
|
|
| 12. |
- Tam, Miguel A., 1976, et al.
(författare)
-
Plasmacytoid dendritic cells mature independently of MyD88 and IFN-alpha beta R in response to Listeria and stimulate CD8 T cells
- 2011
-
Ingår i: IMMUNOLOGY LETTERS. - 0165-2478. ; 138:2, s. 104-112
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract: Plasmacytoid dendritic cells (pDCs) are a subpopulation of dendritic cells specialized in the production of IFN-alpha/beta, particularly during viral infections. In this way pDCs directly impact antiviral immunity and influence T cell activation. However, despite their role as modulators of the immune response, their function as antigen-presenting cells (APCs) remains poorly understood. Indeed, their capacity as APCs during bacterial infections is unexplored. Here we investigate the importance of MyD88 and IFN-alpha/beta in upregulating costimulatory molecules on pDCs during Listeria infection and their impact on activation of naive CD8 T cells. We show that pDCs efficiently upregulate CD80 and CD86 during systemic Listeria infection, yet express lower levels of these molecules than conventional dendritic cells (cDCs). Furthermore, pDCs are able to stimulate CD8 T cell proliferation and IFN-gamma production, although less efficiently than cDCs. Despite these differences, the influence of MyD88 and IFN-alpha/beta on CD80 and CD86 expression on pDCs and cDCs is similar. Thus, our data show for the first time the potential of pDCs to activate CD8 T cells in response to a bacterial infection. (C) 2011 Elsevier B.V. All rights reserved.
|
|
