RT Journal Article T1 Characterization of human fibroblastic reticular cells as potential immunotherapeutic tools A1 Valencia Mahón, Jaris A1 Jiménez Pérez, Eva A1 Martínez, Víctor G. A1 Amo, Beatriz G. del A1 Hidalgo, Laura A1 Entrena Martínez, Ana A1 Martínez Fernández De Sevilla, Lidia A1 Río Gallegos, Francisco José Del A1 Varas Fajardo, Alberto A1 Vicente López, María Ángeles A1 Sacedón Ayuso, Rosa AB Fibroblastic reticular cells (FRCs) are essential players during adaptive immune responses not only as a structural support for the encounter of antigen-presenting cells and naive T lymphocytes but also as a source of modulatory signals. However, little is known about this cell population in humans. To address the phenotypical and functional analysis of human FRCs here we established splenic (SP) and mesenteric lymph node (LN) CD45- CD31- CD90+ podoplanin+ myofibroblastic cell cultures.They shared the phenotypical characteristics distinctive of FRCs, including the expression of immunomodulatory factors and peripheral tissue antigens. Nevertheless, human FRCs also showed particular features, some differing from mouse FRCs, like the lack of nitric oxide synthase (NOS2) expression after interferon (IFN)γstimulation. Interestingly, SP-FRCs expressed higher levels of interleukin (IL)-6, BMP4, CCL2, CXCL12 and Notch molecules, and strongly adapted their functional profile to lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (Poly I:C) and IFNγ stimulation. In contrast, we found higher expression of transforming growth factor (TGF)β and Activin A in LN-FRCs that barely responded via Toll-Like Receptor (TLR)3 and constitutively expressed retinaldehyde dehydrogenase 1 enzyme, absent in SP-FRCs. This study reveals human FRCs can be valuable models to increase our knowledge about the physiology of human secondary lymphoid organs in health and disease and to explore the therapeutic options of FRCs. PB Cross Mark SN 1465-3249 YR 2017 FD 2017 LK https://hdl.handle.net/20.500.14352/17925 UL https://hdl.handle.net/20.500.14352/17925 LA eng NO Valencia Mahón, J., Jiménez Pérez, E., Martínez, V. G. et al. «Characterization of Human Fibroblastic Reticular Cells as Potential Immunotherapeutic Tools». Cytotherapy, vol. 19, n.o 5, mayo de 2017, pp. 640-53. DOI.org (Crossref), https://doi.org/10.1016/j.jcyt.2017.01.010. NO Ministerio de Economía, Comercio y Empresa (España) NO Instituto de Salud Carlos III DS Docta Complutense RD 11 abr 2025