Thymic and lymph node mesenchymal subsets can be derived from PDGFRα/β+Gp38+CD34+ICAM1- vascular adventitial precursors

Katarzyna Maria Sitnik, Kerstin Wendland, Holger Weishaupt, Heli Uronen-Hansson, William Jenkinson, Graham Anderson, Knut Kotarsky, William Winston Agace

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    Abstract

    While discrete Gp38- and Gp38+ mesenchymal populations have previously been described in the lymph nodes (LNs) and in the thymus the putative relationship between LN and thymic mesenchymal cells remains unclear. Here, using transcriptome profiling as well as phenotypic and localization studies we comprehensively assessed the mesenchymal cell subset composition of the LNs and the thymus. We find that while LNs selectively harbored a BP3+ PDGFRα+Gp38+ compartment consisting of CCL21-producing fibroblastic reticular cells (FRC), MAdCAM+ marginal reticular cells (MRC) and CR1_2+ follicular dendritic cells (FDC), both organs were populated by two corresponding subsets of BP3- PDGFRβ+ cells, PDGFRα-Gp38-ITGA7+ pericytes and PDGFRα+Gp38+CD34+ cells localized in the vascular adventitia and in the capsule. Focusing on the thymus as a model organ we obtain evidence that the latter two subsets initially developed from a common PDGFRα/β+Gp38+CD34-ICAM1- embryonic precursor population. Notably, precursor-progeny studies involving transfer of adult thymus- and adipose tissue-derived BP3-Gp38+PDGFRα+CD34+ICAM1- cells into thymic and LN re-aggregate organ grafts uncovered a precursor activity towards not only pericytes but also BP3+ FRC, MRC and FDC and provided evidence of local environmental imprinting of BP3-Gp38+ cells with organ-specific features. Finally, we demonstrate that BP3-Gp38+ mesenchymal cell maintenance/maturation in the thymus requires LTβR signaling while this pathway appeared dispensable for pericyte differentiation. These findings bring novel insights to the understanding of lymphoid mesenchymal cell heterogeneity and implicate an unforeseen role of the vascular adventitia in lymphoid stroma turnover/regeneration.
    Original languageEnglish
    Publication date2015
    Number of pages1
    Publication statusPublished - 2015
    Event1st International Venice Thymus Meeting - San Servolo Island, Italy
    Duration: 9 Apr 201513 Apr 2015

    Conference

    Conference1st International Venice Thymus Meeting
    CountryItaly
    CitySan Servolo Island
    Period09/04/201513/04/2015

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