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Impaired lymphoid o...
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Reijmers, Rogier M
(författare)
Impaired lymphoid organ development in mice lacking the heparan sulfate modifying enzyme glucuronyl C5-epimerase
- Artikel/kapitelEngelska2010
Förlag, utgivningsår, omfång ...
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2010-04-01
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The American Association of Immunologists,2010
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-135453
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-135453URI
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https://doi.org/10.4049/jimmunol.0902200DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Vondenhoff, Mark F R
(författare)
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Roozendaal, Ramon
(författare)
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Kuil, Annemieke
(författare)
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Li, Jin-PingUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)jinpili
(författare)
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Spaargaren, Marcel
(författare)
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Pals, Steven T
(författare)
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Mebius, Reina E
(författare)
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Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Immunology: The American Association of Immunologists184:7, s. 3656-36640022-17671550-6606
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