Transcriptomics

Dataset Information

0

Germinal Center T follicular helper (GC-Tfh) cell impairment in chronic HIV infection involves c-Maf signaling [microarray]


ABSTRACT: We have recently demonstrated that the function of T follicular helper (Tfh) cells obtained from lymph nodes (LN) of HIV-infected individuals is impaired. We found that these cells were unable to provide proper help to germinal center (GC)-B cells, as observed by altered and inefficient anti-HIV antibody response and premature death of memory B cells. The underlying molecular mechanisms of this dysfunction remain poorly defined. Herein, we have used a unique transcriptional approach to identify these molecular defects. We consequently determined the transcriptional profiles of LN GC-Tfh cells following their interactions with LN GC-B cells from HIV-infected and HIV-uninfected individuals, rather than analyzing resting ex-vivo GC-Tfh cells. We observed that proliferating HIV-infected GC-Tfh cells were transcriptionally different than those from HIV-uninfected individuals, displaying a significant downregulation of immune- and GC-Tfh-associated pathways and genes compared to cells from uninfected individuals. Our results strongly demonstrated that MAF (coding for the transcription factor c-Maf) and its upstream signaling pathway mediators (IL6R and STAT3) were significantly downregulated in HIV-infected subjects, which could contribute to the impaired GC-Tfh and GC-B cell functions reported during infection. We further showed that c-Maf function was associated with the adenosine pathway and that the signaling upstream c-Maf could be partially restored by adenosine deaminase -1 (ADA-1) supplementation. Overall, we identified a novel mechanism that contributes to GC-Tfh impairment during HIV infection. Understanding how GC-Tfh function is altered in HIV is crucial and could provide critical information about the mechanisms leading to the development and maintenance of effective anti-HIV antibodies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE175728 | GEO | 2021/07/19

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2021-07-19 | GSE173500 | GEO
2015-09-02 | E-GEOD-69756 | biostudies-arrayexpress
2023-09-13 | GSE196066 | GEO
2023-01-16 | GSE143942 | GEO
2015-09-02 | GSE69756 | GEO
2017-02-09 | GSE77696 | GEO
2016-09-07 | E-GEOD-81382 | biostudies-arrayexpress
2020-06-18 | GSE152714 | GEO
2007-11-11 | E-GEOD-6740 | biostudies-arrayexpress
2014-06-24 | GSE56499 | GEO