{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:19:39Z","timestamp":1789633179455,"version":"build-2803163510"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-95031-9","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T03:08:36Z","timestamp":1744254516000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Functional organotypic human lymph node model with native immune cells benefits from fibroblastic reticular cell enrichment"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4144-9195","authenticated-orcid":false,"given":"Andrew I.","family":"Morrison","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3701-543X","authenticated-orcid":false,"given":"Jesse E.","family":"Kuipers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4422-3807","authenticated-orcid":false,"given":"Henk P.","family":"Roest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0651-5334","authenticated-orcid":false,"given":"Luc J. W.","family":"van der Laan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-4612","authenticated-orcid":false,"given":"Charlotte M.","family":"de Winde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2243-4857","authenticated-orcid":false,"given":"Jasper J.","family":"Koning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3446-6138","authenticated-orcid":false,"given":"Susan","family":"Gibbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0451-7464","authenticated-orcid":false,"given":"Reina E.","family":"Mebius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"95031_CR1","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/s41590-020-0635-3","volume":"21","author":"AT Krishnamurty","year":"2020","unstructured":"Krishnamurty, A. T. & Turley, S. J. Lymph node stromal cells: cartographers of the immune system. Nat. Immunol. 21, 369\u2013380. https:\/\/doi.org\/10.1038\/s41590-020-0635-3 (2020).","journal-title":"Nat. Immunol."},{"key":"95031_CR2","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.immuni.2006.10.011","volume":"25","author":"M Bajenoff","year":"2006","unstructured":"Bajenoff, M. et al. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25, 989\u20131001. https:\/\/doi.org\/10.1016\/j.immuni.2006.10.011 (2006).","journal-title":"Immunity"},{"key":"95031_CR3","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1038\/nri3298","volume":"12","author":"JP Girard","year":"2012","unstructured":"Girard, J. P., Moussion, C. & Forster, R. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nat. Rev. Immunol. 12, 762\u2013773. https:\/\/doi.org\/10.1038\/nri3298 (2012).","journal-title":"Nat. Rev. Immunol."},{"key":"95031_CR4","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1146\/annurev-immunol-031210-101357","volume":"29","author":"R Roozendaal","year":"2011","unstructured":"Roozendaal, R. & Mebius, R. E. Stromal cell-immune cell interactions. Annu. Rev. Immunol. 29, 23\u201343. https:\/\/doi.org\/10.1146\/annurev-immunol-031210-101357 (2011).","journal-title":"Annu. Rev. Immunol."},{"key":"95031_CR5","doi-asserted-by":"publisher","first-page":"110179","DOI":"10.1016\/j.isci.2024.110179","volume":"27","author":"JEG Roet","year":"2024","unstructured":"Roet, J. E. G. et al. Human lymph node fibroblastic reticular cells maintain heterogeneous characteristics in culture. iScience 27, 110179. https:\/\/doi.org\/10.1016\/j.isci.2024.110179 (2024).","journal-title":"iScience"},{"key":"95031_CR6","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1038\/nri2886","volume":"10","author":"SJ Turley","year":"2010","unstructured":"Turley, S. J., Fletcher, A. L. & Elpek, K. G. The stromal and haematopoietic antigen-presenting cells that reside in secondary lymphoid organs. Nat. Rev. Immunol. 10, 813\u2013825. https:\/\/doi.org\/10.1038\/nri2886 (2010).","journal-title":"Nat. Rev. Immunol."},{"key":"95031_CR7","doi-asserted-by":"publisher","first-page":"e2005046","DOI":"10.1371\/journal.pbio.2005046","volume":"16","author":"K Knoblich","year":"2018","unstructured":"Knoblich, K. et al. The human lymph node microenvironment unilaterally regulates T-cell activation and differentiation. PLoS Biol 16, e2005046. https:\/\/doi.org\/10.1371\/journal.pbio.2005046 (2018).","journal-title":"PLoS Biol"},{"key":"95031_CR8","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1158\/2326-6066.CIR-19-0796","volume":"8","author":"J Eom","year":"2020","unstructured":"Eom, J. et al. Distinctive subpopulations of stromal cells are present in human lymph nodes infiltrated with melanoma. Cancer Immunol. Res. 8, 990\u20131003. https:\/\/doi.org\/10.1158\/2326-6066.CIR-19-0796 (2020).","journal-title":"Cancer Immunol. Res."},{"key":"95031_CR9","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.it.2021.07.003","volume":"42","author":"SE Acton","year":"2021","unstructured":"Acton, S. E., Onder, L., Novkovic, M., Martinez, V. G. & Ludewig, B. Communication, construction, and fluid control: lymphoid organ fibroblastic reticular cell and conduit networks. Trends Immunol. 42, 782\u2013794. https:\/\/doi.org\/10.1016\/j.it.2021.07.003 (2021).","journal-title":"Trends Immunol."},{"issue":"1014\u20131028","key":"95031_CR10","doi-asserted-by":"publisher","first-page":"e1016","DOI":"10.1016\/j.immuni.2018.04.006","volume":"48","author":"LB Rodda","year":"2018","unstructured":"Rodda, L. B. et al. Single-cell RNA sequencing of lymph node stromal cells reveals niche-associated heterogeneity. Immunity 48(1014\u20131028), e1016. https:\/\/doi.org\/10.1016\/j.immuni.2018.04.006 (2018).","journal-title":"Immunity"},{"key":"95031_CR11","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.it.2021.08.009","volume":"42","author":"C Grasso","year":"2021","unstructured":"Grasso, C., Pierie, C., Mebius, R. E. & van Baarsen, L. G. M. Lymph node stromal cells: subsets and functions in health and disease. Trends Immunol. 42, 920\u2013936. https:\/\/doi.org\/10.1016\/j.it.2021.08.009 (2021).","journal-title":"Trends Immunol."},{"key":"95031_CR12","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.it.2021.06.006","volume":"42","author":"L Li","year":"2021","unstructured":"Li, L., Wu, J., Abdi, R., Jewell, C. M. & Bromberg, J. S. Lymph node fibroblastic reticular cells steer immune responses. Trends Immunol. 42, 723\u2013734. https:\/\/doi.org\/10.1016\/j.it.2021.06.006 (2021).","journal-title":"Trends Immunol."},{"key":"95031_CR13","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165713","author":"JS Hahnlein","year":"2020","unstructured":"Hahnlein, J. S. et al. Human lymph node stromal cells have the machinery to regulate peripheral tolerance during health and rheumatoid arthritis. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms21165713 (2020).","journal-title":"Int. J. Mol. Sci."},{"issue":"444\u2013463","key":"95031_CR14","doi-asserted-by":"publisher","first-page":"e410","DOI":"10.1016\/j.ccell.2024.02.001","volume":"42","author":"AJ Radtke","year":"2024","unstructured":"Radtke, A. J. et al. Multi-omic profiling of follicular lymphoma reveals changes in tissue architecture and enhanced stromal remodeling in high-risk patients. Cancer Cell 42(444\u2013463), e410. https:\/\/doi.org\/10.1016\/j.ccell.2024.02.001 (2024).","journal-title":"Cancer Cell"},{"key":"95031_CR15","doi-asserted-by":"publisher","first-page":"365","DOI":"10.14573\/altex.2001241","volume":"37","author":"U Marx","year":"2020","unstructured":"Marx, U. et al. Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development. ALTEX. 37, 365\u2013394. https:\/\/doi.org\/10.14573\/altex.2001241 (2020).","journal-title":"ALTEX."},{"key":"95031_CR16","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3389\/fphar.2018.00006","volume":"9","author":"SA Langhans","year":"2018","unstructured":"Langhans, S. A. Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front. Pharmacol. 9, 6. https:\/\/doi.org\/10.3389\/fphar.2018.00006 (2018).","journal-title":"Front. Pharmacol."},{"key":"95031_CR17","doi-asserted-by":"publisher","first-page":"1373186","DOI":"10.3389\/fimmu.2024.1373186","volume":"15","author":"AI Morrison","year":"2024","unstructured":"Morrison, A. I., Sjoerds, M. J., Vonk, L. A., Gibbs, S. & Koning, J. J. In vitro immunity: an overview of immunocompetent organ-on-chip models. Front. Immunol. 15, 1373186. https:\/\/doi.org\/10.3389\/fimmu.2024.1373186 (2024).","journal-title":"Front. Immunol."},{"key":"95031_CR18","doi-asserted-by":"publisher","first-page":"1183286","DOI":"10.3389\/fimmu.2023.1183286","volume":"14","author":"T Ozulumba","year":"2023","unstructured":"Ozulumba, T., Montalbine, A. N., Ortiz-Cardenas, J. E. & Pompano, R. R. New tools for immunologists: models of lymph node function from cells to tissues. Front. Immunol. 14, 1183286. https:\/\/doi.org\/10.3389\/fimmu.2023.1183286 (2023).","journal-title":"Front. Immunol."},{"key":"95031_CR19","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jbiotec.2010.03.001","volume":"148","author":"C Giese","year":"2010","unstructured":"Giese, C. et al. Immunological substance testing on human lymphatic micro-organoids in vitro. J. Biotechnol. 148, 38\u201345. https:\/\/doi.org\/10.1016\/j.jbiotec.2010.03.001 (2010).","journal-title":"J. Biotechnol."},{"key":"95031_CR20","doi-asserted-by":"publisher","first-page":"105741","DOI":"10.1016\/j.isci.2022.105741","volume":"26","author":"MVJ Braham","year":"2023","unstructured":"Braham, M. V. J. et al. A synthetic human 3D in vitro lymphoid model enhancing B-cell survival and functional differentiation. iScience 26, 105741. https:\/\/doi.org\/10.1016\/j.isci.2022.105741 (2023).","journal-title":"iScience"},{"key":"95031_CR21","doi-asserted-by":"publisher","first-page":"e2103241","DOI":"10.1002\/advs.202103241","volume":"9","author":"G Goyal","year":"2022","unstructured":"Goyal, G. et al. Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ-on-a-Chip. Adv. Sci. (Weinh) 9, e2103241. https:\/\/doi.org\/10.1002\/advs.202103241 (2022).","journal-title":"Adv. Sci. (Weinh)"},{"key":"95031_CR22","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20240289","author":"R Jeger-Madiot","year":"2024","unstructured":"Jeger-Madiot, R. et al. Modeling memory B cell responses in a lymphoid organ-chip to evaluate mRNA vaccine boosting. J. Exp. Med. https:\/\/doi.org\/10.1084\/jem.20240289 (2024).","journal-title":"J. Exp. Med."},{"key":"95031_CR23","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s41591-020-01145-0","volume":"27","author":"LE Wagar","year":"2021","unstructured":"Wagar, L. E. et al. Modeling human adaptive immune responses with tonsil organoids. Nat. Med. 27, 125\u2013135. https:\/\/doi.org\/10.1038\/s41591-020-01145-0 (2021).","journal-title":"Nat. Med."},{"issue":"1910\u20131926","key":"95031_CR24","doi-asserted-by":"publisher","first-page":"e1917","DOI":"10.1016\/j.immuni.2023.06.019","volume":"56","author":"JM Kastenschmidt","year":"2023","unstructured":"Kastenschmidt, J. M. et al. Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids. Immunity 56(1910\u20131926), e1917. https:\/\/doi.org\/10.1016\/j.immuni.2023.06.019 (2023).","journal-title":"Immunity"},{"issue":"410\u2013420","key":"95031_CR25","doi-asserted-by":"publisher","first-page":"e414","DOI":"10.1016\/j.stem.2024.01.012","volume":"31","author":"JM Kastenschmidt","year":"2024","unstructured":"Kastenschmidt, J. M. et al. A human lymphoma organoid model for evaluating and targeting the follicular lymphoma tumor immune microenvironment. Cell Stem Cell 31(410\u2013420), e414. https:\/\/doi.org\/10.1016\/j.stem.2024.01.012 (2024).","journal-title":"Cell Stem Cell"},{"key":"95031_CR26","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.coi.2020.03.003","volume":"64","author":"JJ Koning","year":"2020","unstructured":"Koning, J. J. & Mebius, R. E. Stromal cells and immune cells involved in formation of lymph nodes and their niches. Curr. Opin. Immunol. 64, 20\u201325. https:\/\/doi.org\/10.1016\/j.coi.2020.03.003 (2020).","journal-title":"Curr. Opin. Immunol."},{"key":"95031_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207785","author":"G Harle","year":"2020","unstructured":"Harle, G., Kowalski, C., Garnier, L. & Hugues, S. Lymph node stromal cells: mapmakers of t cell immunity. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms21207785 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"95031_CR28","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/nature13814","volume":"514","author":"SE Acton","year":"2014","unstructured":"Acton, S. E. et al. Dendritic cells control fibroblastic reticular network tension and lymph node expansion. Nature 514, 498\u2013502. https:\/\/doi.org\/10.1038\/nature13814 (2014).","journal-title":"Nature"},{"key":"95031_CR29","doi-asserted-by":"publisher","first-page":"273","DOI":"10.4049\/jimmunol.2000873","volume":"206","author":"C Gago da Graca","year":"2021","unstructured":"Gago da Graca, C., van Baarsen, L. G. M. & Mebius, R. E. Tertiary lymphoid structures: diversity in their development, composition, and role. J. Immunol. 206, 273\u2013281. https:\/\/doi.org\/10.4049\/jimmunol.2000873 (2021).","journal-title":"J. Immunol."},{"key":"95031_CR30","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1007\/s13770-023-00609-x","volume":"21","author":"AI Morrison","year":"2024","unstructured":"Morrison, A. I. et al. An organotypic human lymph node model reveals the importance of fibroblastic reticular cells for dendritic cell function. Tissue Eng. Regen Med. 21, 455\u2013471. https:\/\/doi.org\/10.1007\/s13770-023-00609-x (2024).","journal-title":"Tissue Eng. Regen Med."},{"key":"95031_CR31","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3389\/fimmu.2011.00035","volume":"2","author":"AL Fletcher","year":"2011","unstructured":"Fletcher, A. L. et al. Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells. Front. Immunol. 2, 35. https:\/\/doi.org\/10.3389\/fimmu.2011.00035 (2011).","journal-title":"Front. Immunol."},{"key":"95031_CR32","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1251\/bpo62","volume":"5","author":"B Obermaier","year":"2003","unstructured":"Obermaier, B. et al. Development of a new protocol for 2-day generation of mature dendritic cells from human monocytes. Biol. Proced. Online 5, 197\u2013203. https:\/\/doi.org\/10.1251\/bpo62 (2003).","journal-title":"Biol. Proced. Online"},{"key":"95031_CR33","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1002\/cyto.a.24856","volume":"105","author":"JEG Roet","year":"2024","unstructured":"Roet, J. E. G. et al. Unbiased method for spectral analysis of cells with great diversity of autofluorescence spectra. Cytometry A 105, 595\u2013606. https:\/\/doi.org\/10.1002\/cyto.a.24856 (2024).","journal-title":"Cytometry A"},{"key":"95031_CR34","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1084\/jem.20040254","volume":"200","author":"T Katakai","year":"2004","unstructured":"Katakai, T., Hara, T., Sugai, M., Gonda, H. & Shimizu, A. Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes. J. Exp. Med. 200, 783\u2013795. https:\/\/doi.org\/10.1084\/jem.20040254 (2004).","journal-title":"J. Exp. Med."},{"key":"95031_CR35","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/ni1513","volume":"8","author":"A Link","year":"2007","unstructured":"Link, A. et al. Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat. Immunol. 8, 1255\u20131265. https:\/\/doi.org\/10.1038\/ni1513 (2007).","journal-title":"Nat. Immunol."},{"key":"95031_CR36","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/ni.2965","volume":"15","author":"V Cremasco","year":"2014","unstructured":"Cremasco, V. et al. B cell homeostasis and follicle confines are governed by fibroblastic reticular cells. Nat. Immunol. 15, 973\u2013981. https:\/\/doi.org\/10.1038\/ni.2965 (2014).","journal-title":"Nat. Immunol."},{"key":"95031_CR37","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.3389\/fimmu.2019.02458","volume":"10","author":"I Sanz","year":"2019","unstructured":"Sanz, I. et al. Challenges and opportunities for consistent classification of human b cell and plasma cell populations. Front. Immunol. 10, 2458. https:\/\/doi.org\/10.3389\/fimmu.2019.02458 (2019).","journal-title":"Front. Immunol."},{"key":"95031_CR38","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1002\/cyto.a.21112","volume":"79","author":"C Wei","year":"2011","unstructured":"Wei, C., Jung, J. & Sanz, I. OMIP-003: phenotypic analysis of human memory B cells. Cytometry A 79, 894\u2013896. https:\/\/doi.org\/10.1002\/cyto.a.21112 (2011).","journal-title":"Cytometry A"},{"key":"95031_CR39","doi-asserted-by":"publisher","first-page":"302","DOI":"10.3389\/fimmu.2012.00302","volume":"3","author":"DA Kaminski","year":"2012","unstructured":"Kaminski, D. A., Wei, C., Qian, Y., Rosenberg, A. F. & Sanz, I. Advances in human B cell phenotypic profiling. Front. Immunol. 3, 302. https:\/\/doi.org\/10.3389\/fimmu.2012.00302 (2012).","journal-title":"Front. Immunol."},{"key":"95031_CR40","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/nri3846","volume":"15","author":"AL Fletcher","year":"2015","unstructured":"Fletcher, A. L., Acton, S. E. & Knoblich, K. Lymph node fibroblastic reticular cells in health and disease. Nat. Rev. Immunol. 15, 350\u2013361. https:\/\/doi.org\/10.1038\/nri3846 (2015).","journal-title":"Nat. Rev. Immunol."},{"key":"95031_CR41","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.4049\/jimmunol.1402520","volume":"194","author":"FD Brown","year":"2015","unstructured":"Brown, F. D. & Turley, S. J. Fibroblastic reticular cells: organization and regulation of the T lymphocyte life cycle. J. Immunol. 194, 1389\u20131394. https:\/\/doi.org\/10.4049\/jimmunol.1402520 (2015).","journal-title":"J. Immunol."},{"key":"95031_CR42","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/nature04606","volume":"440","author":"LR Shiow","year":"2006","unstructured":"Shiow, L. R. et al. CD69 acts downstream of interferon-alpha\/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 440, 540\u2013544. https:\/\/doi.org\/10.1038\/nature04606 (2006).","journal-title":"Nature"},{"key":"95031_CR43","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/s41590-021-00920-6","volume":"22","author":"VN Kapoor","year":"2021","unstructured":"Kapoor, V. N. et al. Gremlin 1(+) fibroblastic niche maintains dendritic cell homeostasis in lymphoid tissues. Nat. Immunol. 22, 571\u2013585. https:\/\/doi.org\/10.1038\/s41590-021-00920-6 (2021).","journal-title":"Nat. Immunol."},{"key":"95031_CR44","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.it.2011.10.006","volume":"33","author":"JJ Koning","year":"2012","unstructured":"Koning, J. J. & Mebius, R. E. Interdependence of stromal and immune cells for lymph node function. Trends Immunol. 33, 264\u2013270. https:\/\/doi.org\/10.1016\/j.it.2011.10.006 (2012).","journal-title":"Trends Immunol."},{"key":"95031_CR45","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210790","author":"BA Heesters","year":"2021","unstructured":"Heesters, B. A. et al. Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells. J. Exp. Med. https:\/\/doi.org\/10.1084\/jem.20210790 (2021).","journal-title":"J. Exp. Med."},{"key":"95031_CR46","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1084\/jem.20132409","volume":"211","author":"M Jarjour","year":"2014","unstructured":"Jarjour, M. et al. Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells. J. Exp. Med. 211, 1109\u20131122. https:\/\/doi.org\/10.1084\/jem.20132409 (2014).","journal-title":"J. Exp. Med."},{"key":"95031_CR47","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.jdermsci.2024.07.001","volume":"115","author":"E Michielon","year":"2024","unstructured":"Michielon, E. et al. Integration of line-field confocal optical coherence tomography and in situ microenvironmental mapping to investigate the living microenvironment of reconstructed human skin and melanoma models. J. Dermatol. Sci. 115, 85\u201393. https:\/\/doi.org\/10.1016\/j.jdermsci.2024.07.001 (2024).","journal-title":"J. Dermatol. Sci."},{"key":"95031_CR48","doi-asserted-by":"publisher","first-page":"e27618","DOI":"10.1371\/journal.pone.0027618","volume":"6","author":"S Siegert","year":"2011","unstructured":"Siegert, S. et al. Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide. PLoS One 6, e27618. https:\/\/doi.org\/10.1371\/journal.pone.0027618 (2011).","journal-title":"PLoS One"},{"key":"95031_CR49","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/ni.2112","volume":"12","author":"V Lukacs-Kornek","year":"2011","unstructured":"Lukacs-Kornek, V. et al. Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nat. Immunol. 12, 1096\u20131104. https:\/\/doi.org\/10.1038\/ni.2112 (2011).","journal-title":"Nat. Immunol."},{"key":"95031_CR50","doi-asserted-by":"publisher","first-page":"e26138","DOI":"10.1371\/journal.pone.0026138","volume":"6","author":"O Khan","year":"2011","unstructured":"Khan, O. et al. Regulation of T cell priming by lymphoid stroma. PLoS One 6, e26138. https:\/\/doi.org\/10.1371\/journal.pone.0026138 (2011).","journal-title":"PLoS One"},{"key":"95031_CR51","doi-asserted-by":"publisher","first-page":"12139","DOI":"10.1073\/pnas.1412910111","volume":"111","author":"AE Denton","year":"2014","unstructured":"Denton, A. E., Roberts, E. W., Linterman, M. A. & Fearon, D. T. Fibroblastic reticular cells of the lymph node are required for retention of resting but not activated CD8+ T cells. Proc. Natl. Acad. Sci. U. S. A 111, 12139\u201312144. https:\/\/doi.org\/10.1073\/pnas.1412910111 (2014).","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"95031_CR52","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200795","author":"D Kim","year":"2022","unstructured":"Kim, D. et al. Lymph node fibroblastic reticular cells regulate differentiation and function of CD4 T cells via CD25. J. Exp. Med. https:\/\/doi.org\/10.1084\/jem.20200795 (2022).","journal-title":"J. Exp. Med."},{"key":"95031_CR53","doi-asserted-by":"publisher","first-page":"1373537","DOI":"10.3389\/fimmu.2024.1373537","volume":"15","author":"MT Mitul","year":"2024","unstructured":"Mitul, M. T. et al. Tissue-specific sex differences in pediatric and adult immune cell composition and function. Front. Immunol. 15, 1373537. https:\/\/doi.org\/10.3389\/fimmu.2024.1373537 (2024).","journal-title":"Front. Immunol."},{"issue":"430\u2013446","key":"95031_CR54","doi-asserted-by":"publisher","first-page":"e420","DOI":"10.1016\/j.cell.2024.10.042","volume":"188","author":"L Onder","year":"2025","unstructured":"Onder, L. et al. Fibroblastic reticular cells generate protective intratumoral T cell environments in lung cancer. Cell 188(430\u2013446), e420. https:\/\/doi.org\/10.1016\/j.cell.2024.10.042 (2025).","journal-title":"Cell"},{"key":"95031_CR55","doi-asserted-by":"publisher","first-page":"151492","DOI":"10.1016\/j.ijmm.2021.151492","volume":"311","author":"M Zou","year":"2021","unstructured":"Zou, M., Wiechers, C. & Huehn, J. Lymph node stromal cell subsets-emerging specialists for tailored tissue-specific immune responses. Int. J. Med. Microbiol. 311, 151492. https:\/\/doi.org\/10.1016\/j.ijmm.2021.151492 (2021).","journal-title":"Int. J. Med. Microbiol."},{"key":"95031_CR56","doi-asserted-by":"publisher","first-page":"114111","DOI":"10.1016\/j.addr.2022.114111","volume":"182","author":"JH Hammel","year":"2022","unstructured":"Hammel, J. H., Zatorski, J. M., Cook, S. R., Pompano, R. R. & Munson, J. M. Engineering in vitro immune-competent tissue models for testing and evaluation of therapeutics. Adv. Drug Deliv. Rev. 182, 114111. https:\/\/doi.org\/10.1016\/j.addr.2022.114111 (2022).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"95031_CR57","doi-asserted-by":"publisher","first-page":"4273","DOI":"10.4049\/jimmunol.0900835","volume":"183","author":"AA Tomei","year":"2009","unstructured":"Tomei, A. A., Siegert, S., Britschgi, M. R., Luther, S. A. & Swartz, M. A. Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment. J. Immunol. 183, 4273\u20134283. https:\/\/doi.org\/10.4049\/jimmunol.0900835 (2009).","journal-title":"J. Immunol."},{"key":"95031_CR58","doi-asserted-by":"publisher","first-page":"14037","DOI":"10.1021\/acsami.1c02542","volume":"13","author":"YS Choi","year":"2021","unstructured":"Choi, Y. S. et al. Immunomodulatory scaffolds derived from lymph node extracellular matrices. ACS Appl. Mater Interfaces 13, 14037\u201314049. https:\/\/doi.org\/10.1021\/acsami.1c02542 (2021).","journal-title":"ACS Appl. Mater Interfaces"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95031-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95031-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95031-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T03:08:37Z","timestamp":1744254517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95031-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["95031"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-95031-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]},"assertion":[{"value":"3 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12233"}}