Evidence map›Paper›PMID 24572363›Full record

ArticleNature2014

IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases.

Ping Shen, Toralf Roch, Vicky Lampropoulou, Richard A O'Connor, Ulrik Stervbo, Ellen Hilgenberg, Stefanie Ries, Van Duc Dang, Yarúa Jaimes, Capucine Daridon and 21 more

Open access · greenAbstract read
In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 592 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
592citing papers in PubMed, 2 pooled it
42.2field-weighted citation impact, top 1% 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

592 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,002 citations in OpenAlex.

  1. Pooled it
  2. Myocardial Immune Cells: The Basis of Cardiac Immunology.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Pooled it
  3. Trial
  4. Sustained immunotolerance in multiple sclerosis after stem cell transplant.Annals of clinical and translational neurology · 2022
    Trial
  5. Article
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  14. From Tregs to tissue remodelling: FOXP3 and IL-35 in the inflammatory landscape of nasal polyps.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Rethinking MS Therapeutics: From Disease Pathogenesis Mechanisms to AI-Driven Drug Discovery.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Review

532 more citing papers are in PubMed but not listed here.

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

31 authors at 5 institutions in 3 countries.

Ping Shen *Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Toralf Roch *Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Vicky LampropoulouDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Richard A O'ConnorUniversity of Edinburgh, Centre for Inflammation Research and Centre for Multiple Sclerosis Research, Queen's Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom.
Ulrik StervboDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Ellen HilgenbergDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Stefanie RiesDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Van Duc DangDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Yarúa JaimesDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Capucine DaridonDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Rui LiNeuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, H3A2B4, Canada.
Luc JouneauVirologie et Immunologie Moléculaires, INRA, 78352 Jouy-en-Josas, France.
Pierre BoudinotVirologie et Immunologie Moléculaires, INRA, 78352 Jouy-en-Josas, France.
Siska WilantriDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Imme SakwaDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Yusei MiyazakiNeuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, H3A2B4, Canada.
Melanie D LeechUniversity of Edinburgh, Centre for Inflammation Research and Centre for Multiple Sclerosis Research, Queen's Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom.
Rhoanne C McPhersonUniversity of Edinburgh, Centre for Inflammation Research and Centre for Multiple Sclerosis Research, Queen's Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom.
Stefan WirtzMedical Clinic 1, Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, Germany.
Markus NeurathMedical Clinic 1, Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, Germany.
Kai HoehligDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Edgar MeinlInstitut für Klinische Neuroimmunologie Klinikum der Ludwig-Maximilians-Universität München, 81377 München, Germany.
Andreas GrützkauDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Joachim R GrünDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Katharina HornDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Anja A KühlImmunpathologie, Research Center ImmunoSciences, 12203 Berlin, Germany.
Thomas DörnerDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Amit Bar-OrNeuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, H3A2B4, Canada.
Stefan H E KaufmannMax Planck Institute of Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
Stephen M AndertonUniversity of Edinburgh, Centre for Inflammation Research and Centre for Multiple Sclerosis Research, Queen's Medical Research Institute, Edinburgh, EH16 4TJ, United Kingdom.
Simon FillatreauDeutsches Rheuma-Forschungszentrum, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
Charité - Universitätsmedizin Berlin · DEVirologie et Immunologie Moléculaires · FRCentre for Inflammation Research · GBLudwig-Maximilians-Universität München · DEMax Planck Society · DE

Funding

CIHRMedical Research Council G0801924Medical Research Council G0901697Medical Research Council G1100084Wellcome Trust 087833Wellcome Trust 095831
6 · The paper itself

Abstract

B lymphocytes have critical roles as positive and negative regulators of immunity. Their inhibitory function has been associated primarily with interleukin 10 (IL-10) because B-cell-derived IL-10 can protect against autoimmune disease and increase susceptibility to pathogens. Here we identify IL-35-producing B cells as key players in the negative regulation of immunity. Mice in which only B cells did not express IL-35 lost their ability to recover from the T-cell-mediated demyelinating autoimmune disease experimental autoimmune encephalomyelitis (EAE). In contrast, these mice displayed a markedly improved resistance to infection with the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as shown by their superior containment of the bacterial growth and their prolonged survival after primary infection, and upon secondary challenge, compared to control mice. The increased immunity found in mice lacking IL-35 production by B cells was associated with a higher activation of macrophages and inflammatory T cells, as well as an increased function of B cells as antigen-presenting cells (APCs). During Salmonella infection, IL-35- and IL-10-producing B cells corresponded to two largely distinct sets of surface-IgM(+)CD138(hi)TACI(+)CXCR4(+)CD1d(int)Tim1(int) plasma cells expressing the transcription factor Blimp1 (also known as Prdm1). During EAE, CD138(+) plasma cells were also the main source of B-cell-derived IL-35 and IL-10. Collectively, our data show the importance of IL-35-producing B cells in regulation of immunity and highlight IL-35 production by B cells as a potential therapeutic target for autoimmune and infectious diseases. This study reveals the central role of activated B cells, particularly plasma cells, and their production of cytokines in the regulation of immune responses in health and disease.

Indexed as

AnimalsAntigen-Presenting CellsB-LymphocytesCD40 AntigensEncephalomyelitis, Autoimmune, ExperimentalFemaleHumansImmunityInterleukin-10InterleukinsLymphocyte ActivationMacrophagesMaleMicePlasma CellsSalmonella InfectionsCD40 AntigensInterleukin-10interleukin-35, mouseInterleukinsTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID24572363
PMCPMC4260166
OpenAlexW1976302032

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Registered trials

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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.