Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant
Summary: Immunological processes that underpin human immune responses to therapeutics and vaccine components, such as vaccine adjuvants, remain poorly defined due to a paucity of models that faithfully recapitulate immune activation in lymphoid tissues. We describe precision-cut human lymph node (LN...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725007090 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849706587555364864 |
|---|---|
| author | Joannah R. Fergusson Jacqueline H.Y. Siu Nitya Gupta Edward Jenkins Eloise Nee Sören Reinke Tamara Ströbel Ananya Bhalla Shyami M. Kandage Thomas Courant Sarah Hill Moustafa Attar Michael L. Dustin Alex Gordon-Weeks Mark Coles Calliope A. Dendrou Anita Milicic |
| author_facet | Joannah R. Fergusson Jacqueline H.Y. Siu Nitya Gupta Edward Jenkins Eloise Nee Sören Reinke Tamara Ströbel Ananya Bhalla Shyami M. Kandage Thomas Courant Sarah Hill Moustafa Attar Michael L. Dustin Alex Gordon-Weeks Mark Coles Calliope A. Dendrou Anita Milicic |
| author_sort | Joannah R. Fergusson |
| collection | DOAJ |
| description | Summary: Immunological processes that underpin human immune responses to therapeutics and vaccine components, such as vaccine adjuvants, remain poorly defined due to a paucity of models that faithfully recapitulate immune activation in lymphoid tissues. We describe precision-cut human lymph node (LN) slices as a functioning, architecturally preserved, full-organ cross-sectional model system. Using single-cell transcriptomics and multiplexed imaging, we explore early inflammatory response to a potent, clinically relevant liposomal vaccine adjuvant containing a TLR4-agonist and QS-21 saponin. Both TLR4 and NLRP3 inflammasome activation are involved in the direct initiation of the inflammatory response to adjuvant by monocytes and macrophages (Mon./Mac.) with secretion of interleukin (IL)-1β, but not IL-18, dependent on TLR4 signaling. Innate lymphoid cells, including natural killer cells, are indirectly activated by Mon./Mac.-produced cytokines, signaling downstream to B cells via interferon-γ secretion. Resident LN stromal populations, primed both directly and indirectly by vaccine adjuvant, are instrumental in mediating inflammatory cell recruitment, particularly neutrophils. |
| format | Article |
| id | doaj-art-5995ff0b32b84b17a595a34702575abe |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-5995ff0b32b84b17a595a34702575abe2025-08-20T03:16:08ZengElsevierCell Reports2211-12472025-07-0144711593810.1016/j.celrep.2025.115938Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvantJoannah R. Fergusson0Jacqueline H.Y. Siu1Nitya Gupta2Edward Jenkins3Eloise Nee4Sören Reinke5Tamara Ströbel6Ananya Bhalla7Shyami M. Kandage8Thomas Courant9Sarah Hill10Moustafa Attar11Michael L. Dustin12Alex Gordon-Weeks13Mark Coles14Calliope A. Dendrou15Anita Milicic16Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKJenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKVaccine Formulation Institute, Rue du Champ-Blanchod 4, 1228 Plan-Les-Ouates, SwitzerlandKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UKNuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UKKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UK; Corresponding authorKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UK; Corresponding authorJenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK; Corresponding authorSummary: Immunological processes that underpin human immune responses to therapeutics and vaccine components, such as vaccine adjuvants, remain poorly defined due to a paucity of models that faithfully recapitulate immune activation in lymphoid tissues. We describe precision-cut human lymph node (LN) slices as a functioning, architecturally preserved, full-organ cross-sectional model system. Using single-cell transcriptomics and multiplexed imaging, we explore early inflammatory response to a potent, clinically relevant liposomal vaccine adjuvant containing a TLR4-agonist and QS-21 saponin. Both TLR4 and NLRP3 inflammasome activation are involved in the direct initiation of the inflammatory response to adjuvant by monocytes and macrophages (Mon./Mac.) with secretion of interleukin (IL)-1β, but not IL-18, dependent on TLR4 signaling. Innate lymphoid cells, including natural killer cells, are indirectly activated by Mon./Mac.-produced cytokines, signaling downstream to B cells via interferon-γ secretion. Resident LN stromal populations, primed both directly and indirectly by vaccine adjuvant, are instrumental in mediating inflammatory cell recruitment, particularly neutrophils.http://www.sciencedirect.com/science/article/pii/S2211124725007090CP: Immunology |
| spellingShingle | Joannah R. Fergusson Jacqueline H.Y. Siu Nitya Gupta Edward Jenkins Eloise Nee Sören Reinke Tamara Ströbel Ananya Bhalla Shyami M. Kandage Thomas Courant Sarah Hill Moustafa Attar Michael L. Dustin Alex Gordon-Weeks Mark Coles Calliope A. Dendrou Anita Milicic Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant Cell Reports CP: Immunology |
| title | Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant |
| title_full | Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant |
| title_fullStr | Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant |
| title_full_unstemmed | Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant |
| title_short | Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant |
| title_sort | ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725007090 |
| work_keys_str_mv | AT joannahrfergusson exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT jacquelinehysiu exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT nityagupta exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT edwardjenkins exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT eloisenee exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT sorenreinke exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT tamarastrobel exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT ananyabhalla exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT shyamimkandage exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT thomascourant exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT sarahhill exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT moustafaattar exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT michaelldustin exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT alexgordonweeks exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT markcoles exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT calliopeadendrou exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant AT anitamilicic exvivomodeloffunctioninghumanlymphnoderevealsroleforinnatelymphocytesandstromainresponsetovaccineadjuvant |