Evidence map›Paper›PMID 40199322›Full record

ArticleCell2025

Brain-wide mapping of immune receptors uncovers a neuromodulatory role of IL-17E and the receptor IL-17RB.

Yunjin Lee, Tomoe Ishikawa, Hyeseung Lee, Byeongjun Lee, Changhyeon Ryu, Irene Davila Mejia, Minjin Kim, Guangqing Lu, Yujin Hong, Mengyang Feng and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

25 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

18 authors.

Yunjin LeeDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Tomoe IshikawaPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Hyeseung LeePicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Byeongjun LeePicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Changhyeon RyuPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Irene Davila MejiaPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Minjin KimDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Guangqing LuDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Yujin HongDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Mengyang FengPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Hyeyoon ShinDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Sylvain MelocheInstitute for Research in Immunology and Cancer (IRIC), Montreal, QC, Canada.
Richard M LocksleyDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
Ekaterina KoltsovaDepartments of Medicine and Biomedical Sciences, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Sergei I GrivennikovDepartments of Medicine and Biomedical Sciences, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Myriam HeimanPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Gloria B ChoiPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: gbchoi@mit.edu.
Jun R HuhDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Human Biology Microbiome Quantum Research Center (Bio2Q), Keio University, Tokyo, Japan; Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA, USA. Electronic address: jun_huh@hms.harvard.edu.

Funding

Viral ModuleP30EY012196 · NEI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MARGARET S LIVINGSTONE · 1998 to 2026
$21.3M
Bacterial metabolites controlling Th17 cellsR01DK110559 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI HUH, JUN R. · 2016 to 2024
$5.1M
Pregnancy influences maternal immune cell function and fetal brain developmentR01MH119459 · NIMH · HARVARD MEDICAL SCHOOL · PI Jun R. Huh · 2019 to 2026
$3.9M
Elucidating neural substrates that mediate autism-like behaviorsR01MH115037 · NIMH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI CHOI, GLORIA · 2017 to 2021
$2.6M
The role of Interleukin 17RB signaling in colorectal cancer progressionR01CA227629 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI GRIVENNIKOV, SERGEI I · 2018 to 2022
$2.5M
Mechanisms of cytokine driven tumor elicited inflammation in colorectal cancerR01CA218133 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI GRIVENNIKOV, SERGEI I · 2018 to 2022
$2.4M
Cytokine-mediated regulation of immunity and microenvironment in colorectal cancer metastasisR01CA287786 · NCI · CEDARS-SINAI MEDICAL CENTER · PI Sergei I Grivennikov · 2024 to 2026
$2.0M
NCI NIH HHS R01 CA218133NCI NIH HHS R01 CA227629NCI NIH HHS R01 CA287786NEI NIH HHS P30 EY012196NIDDK NIH HHS R01 DK110559NIMH NIH HHS R01 MH115037NIMH NIH HHS R01 MH119459
6 · The paper itself

Abstract

Cytokines interact with their receptor complexes to orchestrate diverse processes-from immune responses to behavioral modulation. Interleukin-17A (IL-17A) mediates protective immune responses by binding to IL-17 receptor A (IL-17RA) and IL-17RC subunits. IL-17A also modulates social interaction, yet the role of cytokine receptors in this process and their expression in the brain remains poorly characterized. Here, we mapped the brain-region-specific expression of all major IL-17R subunits and found that in addition to IL-17RA, IL-17RB-but not IL-17RC-plays a role in social behaviors through its expression in the cortex. We further showed that IL-17E, expressed in cortical neurons, enhances social interaction by acting on IL-17RA- and IL-17RB-expressing neurons. These findings highlight an IL-17 circuit within the cortex that modulates social behaviors. Thus, characterizing spatially restricted cytokine receptor expression can be leveraged to elucidate how cytokines function as critical messengers mediating neuroimmune interactions to shape animal behaviors.

Indexed as

BrainInterleukin-17Receptors, Interleukin-17AnimalsCerebral CortexFemaleMaleMiceMice, Inbred C57BLNeuronsSocial BehaviorIl17ra protein, mouseInterleukin-17Receptors, Interleukin-17autismcytokine receptorIL-17AIL-17E (IL-25)IL-17RBIL-17 receptorsocial interaction

Identifiers

PMID40199322
PMCPMC12063771

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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.