Evidence map›Paper›PMID 41507164›Full record

ArticleNature communications2026

Butyrophilin 2A2 promotes T cell immunoregulation via CD45 phosphatase activation and protects against murine autoimmune glomerulonephritis and pregnancy loss.

Shafat Ali, Anders H Berg, Michifumi Yamashita, Ambart E Covarrubias, Jordan Mundell, Pranali N Shah, Ruan Zhang, Vincent Dupont, Bong-Ha Shin, Shen Yang and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. MX1Journal of translational medicine · 2026
    Article
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

17 authors.

Shafat AliDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Anders H BergDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Michifumi YamashitaDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ambart E CovarrubiasDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-6460-9980
Jordan MundellDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Pranali N ShahDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ruan ZhangComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Vincent DupontDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-4264-494X
Bong-Ha ShinComprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Shen YangDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Madhusudhanarao KatikiDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-4092-9386
Ramachandran MuraliDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-8384-2793
Margareta D PisarskaDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-1096-6506
Ravi ThadhaniDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Peter S HeegerDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Stanley C JordanDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Stan.Jordan@cshs.org.ORCID http://orcid.org/0000-0002-0456-8635
S Ananth KarumanchiDepartment of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. sananth.karumanchi@csmc.edu.ORCID http://orcid.org/0000-0002-2281-6831

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

B7 costimulatory family member Butyrophilin 2A2 (BTN2A2) is predominantly expressed by antigen presenting cells and regulates T cell immunity, but molecular mechanisms are unclear. Using immunoblots analyzing TCR-initiated signaling intermediaries, co-immunoprecipitation studies, confocal microscopy, structural modeling-guided mutational analyses, and microscale thermophoresis, we demonstrate that BTN2A2 directly interacts with CD45RO, resulting in CD45 retention within the immune synapse during TCR activation. Recombinant BTN2A2 increases murine CD4+Foxp3+ regulatory T cells (Treg) and reduces T helper 17 (Th17) cells in vitro through mechanisms dependent on CD45 phosphatase activity. BTN2A2 therapy alleviates disease severity in murine nephrotoxic glomerulonephritis and autoimmune miscarriage while increasing Treg/Th17 ratios. Analyses of BTN2A2-deficient animals show exacerbation of disease associated with reduced Treg/Th17 ratios. BTN2A2 functions analogously on human T cells suppressing Th17, Th1 and Th2 responses while inducing Tregs. Together, our studies identify BTN2A2 as a modulator of CD45RO signaling in T cells, providing insight into how BTN2A2 regulates T cell-dependent immune responses including those mediating autoimmunity and transplant rejection.

Indexed as

Autoimmune DiseasesButyrophilinsGlomerulonephritisLeukocyte Common AntigensAnimalsFemaleHumansMiceMice, Inbred C57BLMice, KnockoutPregnancyReceptors, Antigen, T-CellSignal TransductionTh17 CellsT-Lymphocytes, RegulatoryButyrophilinsLeukocyte Common AntigensPtprc protein, mouseReceptors, Antigen, T-Cell

Identifiers

PMID41507164
PMCPMC12873404

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.