| 1. |
- Nilton, Anna, et al.
(författare)
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Zinc Finger Protein 148 Is Dispensable for Primitive and Definitive Hematopoiesis in Mice
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoiesis is regulated by transcription factors that induce cell fate and differentiation in hematopoietic stem cells into fully differentiated hematopoietic cell types. The transcription factor zinc finger protein 148 (Zfp148) interacts with the hematopoietic transcription factor Gata1 and has been implicated to play an important role in primitive and definitive hematopoiesis in zebra fish and mouse chimeras. We have recently created a gene-trap knockout mouse model deficient for Zfp148, opening up for analyses of hematopoiesis in a conventional loss-of-function model in vivo. Here, we show that Zfp148-deficient neonatal and adult mice have normal or slightly increased levels of hemoglobin, hematocrit, platelets and white blood cells, compared to wild type controls. Hematopoietic lineages in bone marrow, thymus and spleen from Zfp148(gt/gt) mice were further investigated by flow cytometry. There were no differences in T-cells (CD4 and CD8 single positive cells, CD4 and CD8 double negative/positive cells) in either organ. However, the fraction of CD69- and B220-positive cells among lymphocytes in spleen was slightly lower at postnatal day 14 in Zfp148(gt/gt) mice compared to wild type mice. Our results demonstrate that Zfp148-deficient mice generate normal mature hematopoietic populations thus challenging earlier studies indicating that Zfp148 plays a critical role during hematopoietic development.
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| 2. |
- Rolf, Julia, 1979
(författare)
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Genetics and functions of innate-like lymphocyte subsets
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The immune system contains three different branches: innate immunity, adaptive immunity and innate-like lymphocytes that share properties both with the innate and adaptive immune cells. The innate-like lymphocytes have the capacity to rapidly become activated by invading pathogens and also to modulate immune responses and thereby inhibit or promote inflammation. However, understanding of the innate-like lymphocyte properties and functions has remained incomplete. This thesis describes the properties, genetic regulation, gene-expression profile and functional response of innate-like lymphocyte populations in mice. To determine the role of the innate-like B lymphocyte subset called marginal zone (MZ) B cells in autoimmunity this population was studied in the nonobese diabetic (NOD) mouse model of autoimmune diabetes. The MZ B cell population size was expanded compared to the non-autoimmune C57Bl/6 mice. The increase in MZ B cell numbers occurred before autoimmunity was initiated and not as a secondary consequence of diabetes. The MZ B cell population in NOD mice was genetically most strongly associated with diabetes-susceptibility loci Idd9/11 on chromosome 4. In addition to MZ B cells, the innate-like lymphocyte population termed natural killer T (NKT) cells was studied. NKT cells possess potent immunomodulatory functions and are divided into two subsets based on the TCR usage. Microarray technology was utilized for analyzing the global gene expression profile of the two NKT cell subsets in comparison to conventional CD4+ T cells. The NKT cells over-expressed genes encoding NK cell receptors, pro-cytotoxic molecules and chemokine-receptors that promote homing to inflamed tissues. Expression of transcription factors associated with immune cell development, such as Hhex and Id2 was induced already during thymic development. The microarray analysis of the NKT cell subsets has provided profound new insights into their features, transcriptional regulation and potential functions. The functional role of NKT cells in infectious disease was studied during infection by the pathogenic bacteria Salmonella typhimurium. The NKT cells became strongly activated by the ongoing Salmonella infection and participated in fighting Salmonella during the early phase of the infection through production of IFN-gamma. Activation of NKT cells via infection caused by an intracellular pathogen strongly skewed the NKT cells towards IFN-gamma dominated immunity. This thesis explores the properties of innate-like lymphocyte populations, with emphasize on the underlying genetic regulation and global gene expression profile. In addition, the functional role of the NKT cells in the immune response against infection is described.
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| 3. |
- Rolf, Julia, 1979, et al.
(författare)
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Molecular profiling reveals distinct functional attributes of CD1d-restricted natural killer (NK) T cell subsets.
- 2008
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Ingår i: Molecular immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 45:9, s. 2607-20
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Tidskriftsartikel (refereegranskat)abstract
- CD1d-restricted natural killer T (NKT) cells can have multiple effects on an immune response, including the activation, regulation and attraction of innate immune cells, and modulation of adaptive immunity. Recent studies reveal that there are distinct subsets of NKT cells which selectively perform some of the functions attributed to CD1d-restricted cells, but the mechanisms underlying these functional differences have not been resolved. Our aim in this study was to identify novel NKT cell associated traits that would provide important insight into NKT cell activation and function. To this end, we have performed gene expression profiling of two separate subsets of NKT cells, analyzing genes differentially expressed in these cells compared to conventional CD4(+)NK1.1(-) T cells. We identify different sets of genes over expressed in each of the two NKT cell types, as well as genes that are common to the two CD1d-restricted NKT cell populations analyzed. A large number of these genes are highly relevant for NKT cell development, activation and function. Each NKT subtype displayed a unique set of chemokine receptors, integrins and molecules related to effector function, supporting the notion that distinct NKT cells can be selectively engaged and have diverse functions in different types of immune reactions.
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| 4. |
- Song, J., et al.
(författare)
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Extracellular matrix of secondary lymphoid organs impacts on B-cell fate and survival
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 110:31
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Tidskriftsartikel (refereegranskat)abstract
- We describe a unique extracellular matrix (ECM) niche in the spleen, the marginal zone (MZ), characterized by the basement membrane glycoproteins, laminin alpha 5 and agrin, that promotes formation of a specialized population of MZ B lymphocytes that respond rapidly to blood-borne antigens. Mice with reduced laminin alpha 5 expression show reduced MZ B cells and increased numbers of newly formed (NF) transitional B cells that migrate from the bone marrow, without changes in other immune or stromal cell compartments. Transient integrin alpha 6 beta 1-mediated interaction of NF B cells with laminin alpha 5 in the MZ supports the MZ B-cell population, their long-term survival, and antibody response. Data suggest that the unique 3D structure and biochemical composition of the ECM of lymphoid organs impacts on immune cell fate.
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