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Series GSE161160 Query DataSets for GSE161160
Status Public on Dec 21, 2020
Title Targeting Interleukin-2-Inducible T-cell Kinase (ITK) differentiates GVL and GVHD in allo-HSCT
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Allogeneic hematopoietic stem cell transplantation is a potentially curative procedure for many malignant diseases. Donor T cells prevent disease recurrence via graft-versus-leukemia (GVL) effect. Donor T cells also contribute to graft-versus-host disease (GVHD), a debilitating and potentially fatal complication. Novel treatment strategies are needed which allow preservation of GVL effects without causing GVHD. Using murine models, we show that targeting IL-2-inducible T cell kinase (ITK) in donor T cells reduces GVHD while preserving GVL effects. Both CD8+ and CD4+ donor T cells from Itk-/- mice produce less inflammatory cytokines and show decrease migration to GVHD target organs such as the liver and small intestine, while maintaining GVL efficacy against primary B-cell acute lymphoblastic leukemia (B-ALL). Itk-/- T cells exhibit reduced expression of IRF4 and decreased JAK/STAT signaling activity, but upregulating expression of Eomesodermin (Eomes) and preserve cytotoxicity, necessary for GVL effect. Transcriptome analysis indicates that ITK signaling controls chemokine receptor expression during alloactivation, which in turn affects the ability of donor T cells to migrate to GVHD target organs. Our data suggest that inhibiting ITK could be a therapeutic strategy to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.
 
Overall design ITK KO pre-and post transfer and Wildtype pre-and post transfer
 
Contributor(s) Karimi M, Mammadli M
Citation(s) 33324410
Submission date Nov 10, 2020
Last update date Dec 21, 2020
Contact name Adam Tully Waickman
Organization name SUNY Upstate Medical University
Street address 766 Irving Avenue
City Syracuse
State/province New York
ZIP/Postal code 13210
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (15)
GSM4890869 ITK_1_post_S13_R1_001.fastq.gz
GSM4890870 ITK_2_post_S14_R1_001.fastq.gz
GSM4890871 ITK_3_post_S15_R1_001.fastq.gz
Relations
BioProject PRJNA675784
SRA SRP291967

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE161160_Partek_Karimi_Normalization_Normalized_counts.txt.gz 674.1 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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