Evidence map›Paper›PMID 42520795›Full record

ArticleImmunity2026

TCR origin and specificity to environmental or self-antigens on distinct antigen-presenting cells determine peripheral Treg cell differentiation.

Xinxin Chi, Charlotte H Wang, Yollanda Franco Parisotto, William A Nyberg, Vanja Cabric, Adelaide Gelineau, Yi Cao, David L Owen, Jonas Ambjörnsson, Diane Mathis and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Xinxin ChiDepartment of Immunology, Harvard Medical School, Boston, MA, USA.
Charlotte H WangDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Yollanda Franco ParisottoImmuno-Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
William A NybergDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Vanja CabricImmuno-Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Adelaide GelineauDepartment of Immunology, Harvard Medical School, Boston, MA, USA.
Yi CaoDepartment of Immunology, Harvard Medical School, Boston, MA, USA.
David L OwenDepartment of Immunology, Harvard Medical School, Boston, MA, USA.
Jonas AmbjörnssonDepartment of Immunology, Harvard Medical School, Boston, MA, USA.
Diane MathisDepartment of Immunology, Harvard Medical School, Boston, MA, USA.
Justin EyquemDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Chrysothemis C BrownImmuno-Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine Graduate School of Medical Sciences, New York, NY, USA.
Christophe BenoistDepartment of Immunology, Harvard Medical School, Boston, MA, USA. Electronic address: cbdm@hms.harvard.edu.

Funding

TRAINING IN PEDIATRIC GASTROENTEROLOGY &NUTRITIONT32DK007477 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI Scott B Snapper · 1986 to 2026
$13.3M
Acceptance of non-self: Decoding intestinal immune tolerance during early lifeDP2AI171116 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI Chrysothemis Brown · 2022 to 2026
$2.7M
Treg cell diversity and homeostatic controlR01AI150686 · NIAID · HARVARD MEDICAL SCHOOL · PI BENOIST, CHRISTOPHE O. · 2020 to 2024
$2.6M
Gut Treg cells at the microbiome interfaceR01AI182126 · NIAID · HARVARD MEDICAL SCHOOL · PI CHRISTOPHE O. BENOIST · 2025 to 2026
$1.2M
NIAID NIH HHS DP2 AI171116NIAID NIH HHS R01 AI150686NIAID NIH HHS R01 AI182126NIDDK NIH HHS T32 DK007477
6 · The paper itself

Abstract

Peripheral differentiation of regulatory T (pTreg) cells promotes immunological tolerance to obligate non-self, such as food or symbiotic microbes. We examined the relative importance of TCR recognition vs. environmental cues, leveraging CRISPR-based TCR editing of primary T cells with a large TCR panel, assessing pTreg cell differentiation induced by self-, microbial, or dietary antigens. All antigen classes drove stable pTreg cell differentiation, which varied with TCR origin: TCRs derived from Treg cells enabled pTreg cell differentiation more effectively than those from conventional T cells. TCRs recognizing self-, microbial, or dietary antigens elicited distinct pTreg cell phenotypes: Helios⁺, RORγ⁺, or both. Different TCR-antigen pairs established distinct transcriptional programs. These differences traced to the types of antigen-presenting cells (APCs) involved-food-reactive TCRs depended predominantly on RORγ⁺ APCs and self-reactive TCRs depended on conventional dendritic cells. Thus, TCR specificity is a primary determinant of CD4

Indexed as

Antigen-Presenting CellsAutoantigensCell DifferentiationReceptors, Antigen, T-CellT-Lymphocytes, RegulatoryAnimalsDendritic CellsImmune ToleranceMiceMice, Inbred C57BLNuclear Receptor Subfamily 1, Group F, Member 3AutoantigensNuclear Receptor Subfamily 1, Group F, Member 3Receptors, Antigen, T-CellCRISPR TCR editingfood antigenmicrobiota antigenself-antigen, peripheral toleranceTCRTreg differentiation

Identifiers

PMID42520795
PMCPMC13420020

What OpenQuestion holds

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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.