Impaired lymphoid organ development in mice lacking the heparan sulfate modifying enzyme glucuronyl C5-epimerase

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Fältnamn	Indikatorer	Metadata
000		03239naa a2200385 4500
001		oai:DiVA.org:uu-135453
003		SwePub
008		101207s2010 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1354532 URI
024	7	a https://doi.org/10.4049/jimmunol.09022002 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Reijmers, Rogier M4 aut
245	1 0	a Impaired lymphoid organ development in mice lacking the heparan sulfate modifying enzyme glucuronyl C5-epimerase
264		c 2010-04-01
264	1	b The American Association of Immunologists,c 2010
338		a print2 rdacarrier
520		a The development of lymphoid organs depends on cross talk between hematopoietic cells and mesenchymal stromal cells and on vascularization of the lymphoid primordia. These processes are orchestrated by cytokines, chemokines, and angiogenic factors that require tight spatiotemporal regulation. Heparan sulfate (HS) proteoglycans are molecules designed to specifically bind and regulate the bioactivity of soluble protein ligands. Their binding capacity and specificity are controlled by modification of the HS side chain by HS-modifying enzymes. Although HS proteoglycans have been implicated in the morphogenesis of several organ systems, their role in controlling lymphoid organ development has thus far remained unexplored. In this study, we report that modification of HS by the HS-modifying enzyme glucuronyl C5-epimerase (Glce), which controls HS chain flexibility, is required for proper lymphoid organ development. Glce(-/-) mice show a strongly reduced size of the fetal spleen as well as a spectrum of defects in thymus and lymph node development, ranging from dislocation to complete absence of the organ anlage. Once established, however, the Glce(-/-) primordia recruited lymphocytes and developed normal architectural features. Furthermore, Glce(-/-) lymph node anlagen transplanted into wild-type recipient mice allowed undisturbed lymphocyte maturation. Our results indicate that modification of HS by Glce is required for controlling the activity of molecules that are instructive for early lymphoid tissue morphogenesis but may be dispensable at later developmental stages and for lymphocyte maturation and differentiation.
653		a MEDICINE
653		a MEDICIN
700	1	a Vondenhoff, Mark F R4 aut
700	1	a Roozendaal, Ramon4 aut
700	1	a Kuil, Annemieke4 aut
700	1	a Li, Jin-Pingu Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi4 aut0 (Swepub:uu)jinpili
700	1	a Spaargaren, Marcel4 aut
700	1	a Pals, Steven T4 aut
700	1	a Mebius, Reina E4 aut
710	2	a Uppsala universitetb Institutionen för medicinsk biokemi och mikrobiologi4 org
773	0	t Journal of Immunologyd : The American Association of Immunologistsg 184:7, s. 3656-3664q 184:7<3656-3664x 0022-1767x 1550-6606
856	4	u https://www.jimmunol.org/content/jimmunol/184/7/3656.full.pdf
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-135453
856	4 8	u https://doi.org/10.4049/jimmunol.0902200

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Av författaren/redakt...: Reijmers, Rogier ...; Vondenhoff, Mark ...; Roozendaal, Ramo ...; Kuil, Annemieke; Li, Jin-Ping; Spaargaren, Marc ...; visa fler...; Pals, Steven T; Mebius, Reina E; visa färre...

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