Evidence map›Paper›PMID 38489265›Full record

ArticleCell reports2024

Translational genetics identifies a phosphorylation switch in CARD9 required for innate inflammatory responses.

Marta Brandt, Zhifang Cao, Chirag Krishna, Jennifer L Reedy, Xiebin Gu, Richard A Dutko, Blayne A Oliver, Betsabeh Khoramian Tusi, Jihye Park, Lauren Richey and 7 more

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

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 33% 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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Innate immune recognition ofInfection and immunity · 2026
    Article
  2. Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026
    Review
  3. 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 at 4 institutions in 1 country.

Marta BrandtBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Zhifang CaoBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Chirag KrishnaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Jennifer L ReedyDivision of Infectious Disease, Massachusetts General Hospital, Boston, MA 02114, USA.
Xiebin GuCenter for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Richard A DutkoDivision of Infectious Disease, Massachusetts General Hospital, Boston, MA 02114, USA.
Blayne A OliverCenter for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Betsabeh Khoramian TusiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Jihye ParkBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Lauren RicheyTufts Comparative Medicine Services, Tufts University, Boston, MA 02111, USA.
Åsa SegerstolpeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Scott LitwilerCenter for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Elizabeth A CreaseyCenter for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Kimberly L CareyBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jatin M VyasDivision of Infectious Disease, Massachusetts General Hospital, Boston, MA 02114, USA.
Daniel B GrahamBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Ramnik J XavierBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: rxavier@broadinstitute.org.
Broad Institute · USHarvard University · USMassachusetts General Hospital · USTufts University · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Spatial and temporal resolution to dissect cellular circuits controlling intestinal physiology, immunity, and inflammatory pathologiesRC2DK135492 · NIDDK · BROAD INSTITUTE, INC. · PI Caroline Uhler, Ramnik J Xavier · 2023 to 2026
$7.9M
Functional characterization of CARD9 genetic variants in fungal immunityR01AI137325 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI XAVIER, RAMNIK J · 2018 to 2022
$3.5M
Host Responses to Coccidioides by Human Airway EpitheliumR21AI152499 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI VYAS, JATIN M · 2022 to 2023
$462k
NIAID NIH HHS R01 AI137325NIAID NIH HHS R21 AI152499NIDDK NIH HHS P30 DK043351NIDDK NIH HHS RC2 DK135492
6 · The paper itself

Abstract

Population genetics continues to identify genetic variants associated with diseases of the immune system and offers a unique opportunity to discover mechanisms of immune regulation. Multiple genetic variants linked to severe fungal infections and autoimmunity are associated with caspase recruitment domain-containing protein 9 (CARD9). We leverage the CARD9 R101C missense variant to uncover a biochemical mechanism of CARD9 activation essential for antifungal responses. We demonstrate that R101C disrupts a critical signaling switch whereby phosphorylation of S104 releases CARD9 from an autoinhibited state to promote inflammatory responses in myeloid cells. Furthermore, we show that CARD9 R101C exerts dynamic effects on the skin cellular contexture during fungal infection, corrupting inflammatory signaling and cell-cell communication circuits. Card9 R101C mice fail to control dermatophyte infection in the skin, resulting in high fungal burden, yet show minimal signs of inflammation. Together, we demonstrate how translational genetics reveals molecular and cellular mechanisms of innate immune regulation.

Indexed as

CARD Signaling Adaptor ProteinsMycosesAnimalsAntifungal AgentsInflammationMicePhosphorylationSignal TransductionAntifungal AgentsCard9 protein, mouseCARD Signaling Adaptor Proteinsantifungal immune responseCARD9CP: Immunologycytokine signalingdermatophytosisPKCδ

Identifiers

PMID38489265
PMCPMC11008285
OpenAlexW4392769510

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.