Pouillon V.,Institute Of Recherches Interdisciplinaires En Biologie Humaine Et Moleculaire Iribhm |
Pouillon V.,Free University of Colombia |
Marechal Y.,Institute Of Recherches Interdisciplinaires En Biologie Humaine Et Moleculaire Iribhm |
Marechal Y.,Free University of Colombia |
And 7 more authors.
Advances in Biological Regulation | Year: 2013
Mice genetically-deficient for the B isoform of the inositol 1,4,5-trisphosphate 3-kinase (or Itpkb) have a severe defect in thymocytes differentiation and thus lack peripheral T cells. In order to study the functional role of Itpkb in peripheral T cells, we constructed a new mouse where a transgene encoding mouse Itpkb is specifically and transiently expressed in thymocytes of Itpkb-/- mice. This allows a partial rescue of mature thymocyte/T cell differentiation and thus the functional characterization of peripheral T cells lacking Itpkb. We show here that Itpkb-/- CD4+ and CD8+ peripheral T cells present important functional alterations. Indeed, an increased activated/memory phenotype as well as a decreased proliferative capacity and survival were detected in these T cells. These Itpkb-deficient peripheral T cells have also an increased capacity to secrete cytokines upon stimulation. Together, our present results define the important role of Itpkb in peripheral mature T cell fate and function in mouse, suggesting a potential role for Itpkb in autoimmunity. © 2012 Elsevier Ltd. Source
Pernot E.,Institute Of Recherches Interdisciplinaires En Biologie Humaine Et Moleculaire Iribhm |
Pernot E.,Institute Of Biologie Et Of Medecine Moleculaires Ibmm |
Terryn S.,Catholic University of Louvain |
Cheong S.C.,Institute Of Recherches Interdisciplinaires En Biologie Humaine Et Moleculaire Iribhm |
And 20 more authors.
Pflugers Archiv European Journal of Physiology | Year: 2011
Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5-phosphatase in mice and cells overexpressing the 42-kDa mouse Inpp5k protein. Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin. These defects are associated with the expression of the Inpp5k transgene in renal collecting ducts and with alterations in the arginine vasopressin/aquaporin-2 signalling pathway in this tubular segment. Analysis in a mouse collecting duct mCCD cell line revealed that Inpp5k overexpression leads to increased expression of the arginine vasopressin receptor type 2 and increased cAMP response to arginine vasopressin, providing a basis for increased aquaporin-2 expression and plasma membrane localization with increased osmotically induced water transport. Altogether, our results indicate that Inpp5k 5-phosphatase is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting ducts. © 2011 Springer-Verlag. Source