The role of SOCS3 in modulating leukaemia inhibitory factor signalling during murine placental development
Author(s)
Boyle, K; Robb, L;
Details
Publication Year 2008-01,Volume 77,Issue #1,Page 1-6
Journal Title
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Publication Type
Journal Article
Abstract
Cytokines are an integral part of the adaptive and innate immune responses. The signalling pathways triggered by receptor engagement translate exposure to cytokine into a coordinated biological response. To contain these responses, the initiation, duration and magnitude of the signal is controlled at multiple levels. Suppressor of cytokine signalling (SOCS) proteins act in a negative feedback loop to inhibit signal transduction. Mice with a deletion of SOCS3 die at midgestion due to placental insufficiency. SOCS3-null placentae have increased numbers of mature trophoblast giant cells, disruption of the labyrinthine layer and a decrease in the spongiotrophoblast layer. Genetic crosses have revealed that the phenotype is due to dysregulation of signalling downstream of the leukaemia inhibitory factor (LIF) receptor alpha (LIFR alpha) and that the ligand responsible for this, LIF, is produced by embryonic tissues and acts in a paracrine fashion. These observations highlight the role of LIF as an extrinsic factor regulating trophoblast differentiation in vivo. The creation of mice with conditional deletion of SOCS3 in different tissues has also uncovered critical roles for SOCS3 in the regulation of IL-6, G-CSF and leptin signalling. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
Publisher
ELSEVIER IRELAND LTD
Keywords
DIET-INDUCED OBESITY; CYTOKINE SIGNALING-3; INFLAMMATORY ARTHRITIS; NEGATIVE REGULATOR; LEPTIN SENSITIVITY; INSULIN-RESISTANCE; FACTOR-RECEPTOR; STEM-CELLS; SH2 DOMAIN; BOX MOTIF
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Creation Date: 2008-01-01 12:00:00
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