  Developmental regulation of the composite CAG promoter activity in the murine T lymphocyte cell lineage.; ; Schurmans, Stéphane  et alin Genesis (New York, N.Y. : 2000) (2009), 47 Promoter selection is of utmost importance for the study of in vivo gene function using transgenic models. In the present study, we have analyzed the expression of the GFP marker under the control of the ... [more ▼] Promoter selection is of utmost importance for the study of in vivo gene function using transgenic models. In the present study, we have analyzed the expression of the GFP marker under the control of the composite CAG promoter in the lymphoid compartment of several transgenic mouse strains. Despite the ability of the CAG promoter to drive gene expression in almost all tissues examined to date, its activity appears to be developmentally regulated within the T lymphocyte cell lineage. In particular, CD4 and CD8-expressing, thymic immature T cells displayed lower levels of the GFP marker when compared with both bone marrow precursors and mature circulating T cells, suggesting a transient downregulation of CAG activity during T cell development. Alternative promoters may therefore be preferred for the study of T cell development in vivo using a transgenic approach. [less ▲] Detailed reference viewed: 64 (15 ULg)Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells.; ; et al in Proceedings of the National Academy of Sciences of the United States of America (2007), 104 The contribution of the B isoform of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P(4)], its reaction product, to B cell function ... [more ▼] The contribution of the B isoform of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P(4)], its reaction product, to B cell function and development remains unknown. Here, we show that mice deficient in Itpkb have defects in B cell survival leading to specific and intrinsic developmental alterations in the B cell lineage and antigen unresponsiveness in vivo. The decreased B cell survival is associated with a decreased phosphorylation of Erk1/2 and increased Bim gene expression. B cell survival, development, and antigen responsiveness are normalized in parallel to reduced expression of Bim in Itpkb(-/-) Bim(+/-) mice. Analysis of the signaling pathway downstream of Itpkb revealed that Ins(1,3,4,5)P(4) regulates subcellular distribution of Rasa3, a Ras GTPase-activating protein acting as an Ins(1,3,4,5)P(4) receptor. Together, our results indicate that Itpkb and Ins(1,3,4,5)P(4) mediate a survival signal in B cells via a Rasa3-Erk signaling pathway controlling proapoptotic Bim gene expression [less ▲] Detailed reference viewed: 18 (4 ULg)STAT5 is an Ambivalent Regulator of Neutrophil HomeostasisFievez, Laurence ; Desmet, Christophe ; et alPoster (2007) Detailed reference viewed: 13 (9 ULg)Inositol 1,3,4,5-tetrakisphosphate is essential for normal T lymphocyte development; ; et al in Nature Immunology (2003), 4 Inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) is phosphorylated by Ins(1,4,5)P(3) 3-kinase, generating inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P(4)). The physiological function of Ins(1,3,4,5)P(4 ... [more ▼] Inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) is phosphorylated by Ins(1,4,5)P(3) 3-kinase, generating inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P(4)). The physiological function of Ins(1,3,4,5)P(4) is still unclear, but it has been reported to be a potential modulator of calcium mobilization. Disruption of the gene encoding the ubiquitously expressed Ins(1,4,5)P(3) 3-kinase isoform B (Itpkb) in mice caused a severe T cell deficiency due to major alterations in thymocyte responsiveness and selection. However, we were unable to detect substantial defects in Ins(1,4,5)P(3) amounts or calcium mobilization in Itpkb(-/-) thymocytes. These data indicate that Itpkb and Ins(1,3,4,5)P(4) define an essential signaling pathway for T cell precursor responsiveness and development [less ▲] Detailed reference viewed: 21 (6 ULg)Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo.; ; et al in Journal of Experimental Medicine (1996), 184(4), 1413-24 Dendritic cells (DC) are described as "nature's adjuvant," since they have the capacity to sensitize T cells in vivo upon first encounter with the antigen. The potent accessory properties of DC appear to ... [more ▼] Dendritic cells (DC) are described as "nature's adjuvant," since they have the capacity to sensitize T cells in vivo upon first encounter with the antigen. The potent accessory properties of DC appear to develop sequentially. In particular, the ability to process antigens and to sensitize native T cells develops in sequence, a process termed "maturation" that is well described in vitro. Here, we obtain evidence for maturation in vivo in response to the bacterial product lipopolysaccharide (LPS). Before LPS treatment, many DC are found at the margin between the red and white pulp. These cells lack the M342 and DEC-205 markers, but process soluble proteins effectively. 6 h after LPS, DC with the M342 and DEC-205 markers are found in increased numbers in the T cell areas. These cells have a reduced capacity to process proteins, but show increases in the B7 costimulator and T cell stimulatory capacity. 48 h after LPS, the number of DC in the spleen is reduced markedly. We interpret these findings to mean that LPS can cause DC in the marginal zone to mature and to migrate into and then out of the T cell areas. [less ▲] Detailed reference viewed: 26 (0 ULg) |
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