Exploring the role of CD248/endosialin/TEM-1 on lymphoid stromal cells in secondary lymphoid organs

[摘要] CD248 is a pericyte-associated, mesenchymal stem cell (MSC) marker that is highly expressed during embryological life. This expression is down regulated during development, becoming restricted on lymphoid stroma to the capsule, but reappearing during inflammation, as well as in a number of disease states (Lax et al., 2007). CD248 has been shown to play a role in controlling the differentiation ofMSCto osteoblasts, both in vitro and in vivo, achieving this effect by modulating PDGFRsignalling, as treatment with the PDGFRinhibitorimatinib mesylate phenocopies the effects seen in the CD248·;. mouse (Naylor et al., 2012). Here we present evidence that CD248 is involved in the differentiation of MSC, via PDGFRsignalling,into lymphoid stromaprogenitors bothinvitroandinvivo.Inadultmiceexpression ofCD248is detected onFDCsfollowing immunisation. Using CD248·1- mice, we observe that FDC networks in CD248·1- mice do not form normally and lack the reticular, dendrite-like structure typical ofFDCs. This defect associates with a reduction in the functionality of the germinal centres. Embryonic development of lymph node stroma occurs in a stepwise manner with progressive upregulation of VCAM and ICAM on resident mesenchyme. In the adult stroma, recent work has established links between different stromal cell subtypes; Jarjour eta/. (2014) used a fate mapping technique to discover that marginal reticular cells are able to differentiate to follicular dendritic cells in response to immune challenge. Contrasting evidence shows that FDC in the spleen derive from ubiquitous perivascular precursors, likely to be pericytes (Krautler et al., 2012)

[发布机构] University:University of Birmingham;Department:Institute of Inflammation and Ageing

[关键词] Q Science;QH Natural history;QH301 Biology