Evidence map›Paper›PMID 32114393›Full record

ArticleEBioMedicine2020

Complex human adenoid tissue-based ex vivo culture systems reveal anti-inflammatory drug effects on germinal center T and B cells.

Angelika Schmidt, Johanna E Huber, Özen Sercan Alp, Robert Gürkov, Christoph A Reichel, Matthias Herrmann, Oliver T Keppler, Thomas Leeuw, Dirk Baumjohann

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.6field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. CD9Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  10. Effect of DMARDs on the immunogenicity of vaccines.Nature reviews. Rheumatology · 2023
    Review
  11. Review
  12. Naive and memory CD4iScience · 2022
    Article
  13. Article
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Angelika SchmidtInstitute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Planegg-Martinsried, Germany. Electronic address: Schmidt_Angelika@outlook.com.
Johanna E HuberInstitute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Planegg-Martinsried, Germany.
Özen Sercan AlpR&D, TA Immunology & Inflammation Research, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
Robert GürkovDepartment of Otorhinolaryngology, University Hospital, LMU Munich, 81377 Munich, Germany.
Christoph A ReichelDepartment of Otorhinolaryngology, University Hospital, LMU Munich, 81377 Munich, Germany; Walter Brendel Centre of Experimental Medicine, University Hospital, LMU Munich, 81377 Munich, Germany.
Matthias HerrmannR&D, TA Immunology & Inflammation Research, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
Oliver T KepplerMax von Pettenkofer Institute & Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU Munich, 80336 Munich, Germany.
Thomas LeeuwR&D, TA Immunology & Inflammation Research, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
Dirk BaumjohannInstitute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Planegg-Martinsried, Germany; Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany. Electronic address: dirk.baumjohann@uni-bonn.de.
Ludwig-Maximilians-Universität München · DESanofi (Germany) · DELMU Klinikum · DEUniversity Hospital Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHuman immunology research is often limited to peripheral blood. However, there are important differences between blood immune cells and their counterparts residing in secondary lymphoid organs, such as in the case of germinal center (GC) T follicular helper (Tfh) cells and GC B cells.

methodsWe developed a versatile ex vivo lymphoid organ culture platform that is based on human pharyngeal tonsils (adenoids) and allows for drug testing. We systematically phenotyped Tfh and GC B cell subsets in explant- and suspension cultures using multicolor flow cytometry and cytokine multiplex analysis.

findingsPhenotypic changes of certain ex vivo cultured immune cell subsets could be modulated by cytokine addition. Furthermore, we optimized an activation-induced marker assay to evaluate the response to T cell stimulation. We provide proof-of-concept that Tfh and GC B cells could be modulated in these cultures by different anti-inflammatory drugs in unstimulated states and upon activation with vaccine-derived antigens. For example, GC B cells were lost upon CD40L blockade, and clinically approved JAK inhibitors impacted Tfh and GC B cells, including down-regulation of their key transcription factor BCL6. BCL6 regulation was affected by IL-6 signaling in T cells and IL-4 in B cells, respectively. Furthermore, we demonstrated that JAK signaling and TNF signaling contributed to the stimulation-induced activation of tonsil-derived T cells.

interpretationOur optimized methods, assays, and mechanistic findings can contribute to a better understanding of human GC responses. These insights may be relevant for improving autoimmune disease therapy and vaccination efficacy.

fundingThis work was supported by a project grant under the joint research cooperation agreement of LMU Munich, LMU University Hospital, and Sanofi-Aventis Deutschland GmbH, as well as by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Emmy Noether Programme BA 5132/1-1 and BA 5132/1-2 (252623821), SFB 1054 Project B12 (210592381), and SFB 914 Project B03 (165054336).

Indexed as

AdenoidsAnti-Inflammatory AgentsB-LymphocytesCells, CulturedChildChild, PreschoolGerminal CenterHumansImmunophenotypingInterleukinsJanus KinasesProto-Oncogene Proteins c-bcl-6T Follicular Helper CellsTissue Culture TechniquesTumor Necrosis Factor-alphaAnti-Inflammatory AgentsBCL6 protein, humanInterleukinsJanus KinasesProto-Oncogene Proteins c-bcl-6Tumor Necrosis Factor-alphaActivation-induced marker assay (AIM)BCL6CXCR5Germinal center (GC)Human ex vivo lymphoid tissue cultureImmunotherapyJAK inhibitorT follicular helper cells (Tfh)

Identifiers

PMID32114393
PMCPMC7049648
OpenAlexW3008488708

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.