PXD066986

PXD066986 is an original dataset announced via ProteomeXchange.

Title	JAK inhibitors alleviate EGFRi-induced diarrhea by protecting intestinal stem cells from adaptive immune- exacerbated injury
Description	While intestinal stem cells (ISCs) are essential for epithelial homeostasis, their dynamic regulation during immune-mediated injury remains undefined. Jejunal intestinal stem cell (ISC) proliferative suppression emerges as a pathological hallmark of oral EGFR tyrosine kinase inhibitors (TKIs), propelling chemokine-directed migration of T/B lymphocytes from Peyer's patches. Genetic ablation of adaptive immunity reversed ISC suppression and accelerated mucosal repair. Spatial transcriptomics revealed enhanced ISC-adaptive immune cell crosstalk in the jejunum. Ex vivo modeling demonstrated activated T cells directly impair ISC survival through IFN-γ and TNF-α, with JAK/STAT signaling constituting the critical downstream effector. Targeted JAK inhibition prevented T/B cell-mediated pathology while exhibiting dual efficacy: mitigating EGFRi–induced diarrhea without substantially compromising antitumor efficacy. This work redefines TKI-induced enteropathy as an immune-driven pathology and identifies JAK inhibition as the first mechanism-based supportive therapy, establishing a paradigm for precision management of targeted therapy toxicities.
HostingRepository	iProX
AnnounceDate	2025-08-06
AnnouncementXML	Submission_2025-08-06_00:36:46.494.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuan Cheng
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-06 00:34:40	ID requested
⏵ 1	2025-08-06 00:36:46	announced

Dataset with its publication pending

submitter keyword: Epidermal growth factor receptor inhibitor (EGFRi)

Intestinal stem cells

Adaptive immune

Jak-stat

Shiyi Zhang
contact affiliation	School of Biomedical Engineering, Shanghai Jiao Tong University
contact email	zhangshiyi@sjtu.edu.cn
lab head
Yuan Cheng
contact affiliation	School of Biomedical Engineering, Shanghai Jiao Tong University
contact email	chengyuan_nn@163.com
dataset submitter

iProX dataset URI