title: Context-Dependent Development of Lymphoid Stroma from Adult CD34(+) Adventitial Progenitors.
abstract: Despite the key role of primary and secondary lymphoid organ stroma in immunity, our understanding of the heterogeneity and ontogeny of these cells remains limited. Here, we identify a functionally distinct subset of BP3(-)PDPN(+)PDGFRβ(+)/α(+)CD34(+) stromal adventitial cells in both lymph nodes (LNs) and thymus that is located within the vascular niche surrounding PDPN(-)PDGFRβ(+)/α(-)Esam-1(+)ITGA7(+) pericytes. CD34(+) adventitial cells developed in late embryonic thymus and in postnatal LNs and in the thymus originated, along with pericytes, from a common anlage-seeding progenitor population. Using lymphoid organ re-aggregate grafts, we demonstrate that adult CD34(+) adventitial cells are capable of differentiating into multiple lymphoid stroma-like subsets including pericyte-, FRC-, MRC-, and FDC-like cells, the development of which was lymphoid environment-dependent. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34(+) adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues.
authors.affiliation: Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Bülowsvej 27, 1870 Frederiksberg C, Denmark. Electronic address: kasit@vet.dtu.dk.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Sitnik
authors.affiliation: Immunology Section, Lund University, BMC D14, 221-84 Lund, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wendland
authors.affiliation: Department of Immunology, Genetics, and Pathology, Rudbecklaboratoriet, Uppsala University, 751-85 Uppsala, Sweden.
authors.forename: Holger
authors.initials: H
authors.lastname: Weishaupt
authors.affiliation: Immunology Section, Lund University, BMC D14, 221-84 Lund, Sweden.
authors.forename: Heli
authors.initials: H
authors.lastname: Uronen-Hansson
authors.affiliation: Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: White
authors.affiliation: Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.affiliation: Immunology Section, Lund University, BMC D14, 221-84 Lund, Sweden.
authors.forename: Knut
authors.initials: K
authors.lastname: Kotarsky
authors.affiliation: Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Bülowsvej 27, 1870 Frederiksberg C, Denmark; Immunology Section, Lund University, BMC D14, 221-84 Lund, Sweden. Electronic address: william.agace@med.lu.se.
authors.forename: William W
authors.initials: WW
authors.lastname: Agace
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D036541:ADP-ribosyl Cyclase; D015703:Antigens, CD; D018952:Antigens, CD34; D058851:GPI-Linked Proteins; D053259:Lymphotoxin beta Receptor; D008562:Membrane Glycoproteins; D020797:Receptor, Platelet-Derived Growth Factor beta; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C505699:Ltbr protein, mouse; C087521:ADP-ribosyl cyclase 2