Evidence map›Paper›PMID 33333021›Full record

ArticleCell2021

Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential.

Siyi Huang, Carly G K Ziegler, John Austin, Najat Mannoun, Marko Vukovic, Jose Ordovas-Montanes, Alex K Shalek, Ulrich H von Andrian

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% 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

127 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026
    Review
  10. Review
  11. Nociceptor neurons shape antiviral immunity.Journal of neuroinflammation · 2026
    Review
  12. Review
  13. Article
  14. Neuro-tumor interactions in peripheral tumors.Cancer metastasis reviews · 2026
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Skin innervation and itsFrontiers in cellular neuroscience · 2026
    Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Siyi HuangThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology & HMS Center for Immune Imaging, Harvard Medical School, Boston, MA 02115, USA. Electronic address: siyi_huang@hms.harvard.edu.
Carly G K ZieglerThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Institute for Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Program in Health Sciences and Technology, Harvard Medical School, Cambridge, MA 02139, USA; Harvard Graduate Program in Biophysics, Harvard University, Boston, MA 02115, USA.
John AustinThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology & HMS Center for Immune Imaging, Harvard Medical School, Boston, MA 02115, USA.
Najat MannounThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology & HMS Center for Immune Imaging, Harvard Medical School, Boston, MA 02115, USA.
Marko VukovicThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Institute for Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jose Ordovas-MontanesThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Institute for Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Gastroenterology, Boston Children's Hospital, Boston, MA 02115, USA.
Alex K ShalekThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology & HMS Center for Immune Imaging, Harvard Medical School, Boston, MA 02115, USA; Institute for Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Program in Health Sciences and Technology, Harvard Medical School, Cambridge, MA 02139, USA. Electronic address: shalek@mit.edu.
Ulrich H von AndrianThe Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology & HMS Center for Immune Imaging, Harvard Medical School, Boston, MA 02115, USA. Electronic address: uva@hms.harvard.edu.
Ragon Institute of MGH, MIT and Harvard · USHarvard University · USBroad Institute · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Center for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9M
TRANSFUSION BIOLOGY AND MEDICINET32HL066987 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI JOHN P MANIS · 2001 to 2026
$10.2M
"Bottom - Up" Profiling of Interacting Cellular SystemsDP2GM119419 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHALEK, ALEX K · 2015 to 2015
$2.3M
Regulation of Skin Inflammation by Nociceptive Sensory NeuronsR01AR068383 · NIAMS · HARVARD MEDICAL SCHOOL · PI VON ANDRIAN, ULRICH H · 2015 to 2019
$1.9M
Howard Hughes Medical Institute DRG-2274-16NHGRI NIH HHS RM1 HG006193NHLBI NIH HHS T32 HL066987NIAMS NIH HHS R01 AR068383NIGMS NIH HHS DP2 GM119419NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

Barrier tissue immune responses are regulated in part by nociceptors. Nociceptor ablation alters local immune responses at peripheral sites and within draining lymph nodes (LNs). The mechanisms and significance of nociceptor-dependent modulation of LN function are unknown. Using high-resolution imaging, viral tracing, single-cell transcriptomics, and optogenetics, we identified and functionally tested a sensory neuro-immune circuit that is responsive to lymph-borne inflammatory signals. Transcriptomics profiling revealed that multiple sensory neuron subsets, predominantly peptidergic nociceptors, innervate LNs, distinct from those innervating surrounding skin. To uncover LN-resident cells that may interact with LN-innervating sensory neurons, we generated a LN single-cell transcriptomics atlas and nominated nociceptor target populations and interaction modalities. Optogenetic stimulation of LN-innervating sensory fibers triggered rapid transcriptional changes in the predicted interacting cell types, particularly endothelium, stromal cells, and innate leukocytes. Thus, a unique population of sensory neurons monitors peripheral LNs and may locally regulate gene expression.

Indexed as

ImmunomodulationAction PotentialsAnimalsInflammationLymph NodesMiceNociceptorsOptogeneticsPeptidesSensory Receptor CellsSkinSympathetic Nervous SystemToll-Like ReceptorsPeptidesToll-Like Receptorslymph nodeneuro-immunologynociceptoroptogeneticssensory neuronsingle-cell RNA-seq

Identifiers

PMID33333021
PMCPMC9612289
OpenAlexW3112361808

What OpenQuestion holds

Textmetadata
LicenceTDM
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.