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Series GSE253769 Query DataSets for GSE253769
Status Public on Mar 04, 2024
Title Autophagy-enhancing ATG16L1 polymorphism improves clinical outcomes and promotes superior T-cell immunity in chronic HIV-1 infection
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Chronic HIV-1 infection is characterized by T-cell dysregulation that is partly restored by antiretroviral therapy. Autophagy is a critical regulator of T-cell function. Here, we demonstrate a protective role for autophagy in HIV-1 disease pathogenesis. Targeted analysis of genetic variation in core autophagy gene ATG16L1 revealed the previously unidentified rs6861 polymorphism, which correlated functionally with enhanced autophagy and clinically with improved survival of untreated HIV-1-infected individuals. T cells carrying ATG16L1 rs6861(TT) genotype displayed superior antiviral immunity, evidenced by increased proliferation, revamped immune responsiveness and suppressed exhaustion/immunosenescence features. In-depth flow-cytometric and transriptional profiling revealed T-helper-cell-signatures unique to rs6861(TT) individuals with enriched regulation of pro-inflammatory networks and skewing towards immunoregulatory phenotype. Therapeutic enhancement of autophagy recapitulated the rs6861(TT)-associated traits in non-carriers. These data underscore the in vivo relevance of autophagy for longer-lasting T-cell-mediated HIV-1 control, with implications towards development of host-directed antivirals targeting autophagy to restore immune function in chronic HIV-1 infection.
 
Overall design We performed differential gene expression and gene-set enrichment analyses using data obtained from RNA-seq of fluorescence-activated cell-sorted T cells (CD3+CD4+CD8-) from n=4 rs6861(TT) n=4 rs6861(CC) genotyped individuals under 4 conditions (untreated [steady-state], or stimulated with anti-CD3/anti-CD28, anti-CD3/anti-CD28/IL-15, or anti-CD3/anti-CD28/IL-7 for 16 hours).
 
Contributor(s) Schreurs RR, Koulis A, Booiman T, Boeser-Nunnink B, Cloherty AP, Rader AG, Patel KS, Kootstra NA, Ribeiro CM
Citation(s) 38548722
Submission date Jan 20, 2024
Last update date Apr 04, 2024
Contact name Carla Ribeiro
E-mail(s) c.m.ribeiro@amsterdamumc.nl
Organization name Amsterdam UMC
Department Experimental Immunology
Lab Autophagy-directed Immunity
Street address Meibergdreef 9
City Amsterdam
ZIP/Postal code 1105AZ
Country Netherlands
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (32)
GSM8027660 CD4T cells, rs6861(CC) genotyped donor 1, untreated
GSM8027661 CD4T cells, rs6861(CC) genotyped donor 1, anti-CD3/CD28
GSM8027662 CD4T cells, rs6861(CC) genotyped donor 1, anti-CD3/CD28/IL-15
Relations
BioProject PRJNA1067099

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Supplementary file Size Download File type/resource
GSE253769_Expression_normalized_CPM_all_samples.txt.gz 1.5 Mb (ftp)(http) TXT
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