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Dominant interfering CARD11 variants disrupt JNK signaling to promote GATA3 expression in T cells

ABSTRACT: Dominant interfering CARD11 variants disrupt JNK signaling to promote GATA3 expression in T cells

PROVIDER: PRJNA1217020 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32173600_1.fastq.gz	Fastqsanger.gz
	SRR32173600_2.fastq.gz	Fastqsanger.gz
	SRR32173601_1.fastq.gz	Fastqsanger.gz
	SRR32173601_2.fastq.gz	Fastqsanger.gz
	SRR32173602_1.fastq.gz	Fastqsanger.gz

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Dominant interfering CARD11 variants disrupt JNK signaling to promote GATA3 expression in T cells

Project description:Several “primary atopic disorders” are linked to monogenic defects that attenuate TCR signaling, favoring T helper 2 (TH2) cell differentiation. Patients with CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease suffer from severe atopy, caused by germline loss-of-function/dominant interfering (LOF/DI) CARD11 variants. The CARD11 scaffold enables TCR-induced activation of NF-κB, mTORC1, and JNK signaling, yet the function of CARD11-dependent JNK signaling in T cells remains nebulous. Here we show that CARD11 is critical for TCR-induced activation of JNK1 and JNK2, as well as canonical JUN/FOS AP-1 family members. Patient-derived CARD11 DI variants attenuated wild-type CARD11 JNK signaling, mirroring effects on NF-κB. Transcriptome profiling revealed JNK inhibition upregulated TCR-induced expression of GATA3 and NFATC1, key transcription factors for TH2 cell development. Further, impaired CARD11-JNK signaling was linked to enhanced GATA3 expression in CADINS patient T cells. Our findings reveal a novel intrinsic mechanism connecting impaired CARD11-dependent JNK signaling to enhanced GATA3/NFAT2 induction and TH2 cell differentiation in CADINS patients.

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QRICH1 Mediates an Intracellular Checkpoint for CD8+ T Cell Activation via the CARD11 Signalosome

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OCI-Ly3 CARD11 shRNA

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GATA3 mutation disrupts functional network governed by Estrogen receptor, FOXA1 and GATA3

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OCI-Ly3 CARD11 shRNA

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