Elevated CD153 Expression on Aged T Follicular Helper Cell is Vital for B cell Responses.
Alyssa L ThomasJoseph A WaymanMaha AlmananAnthony T BejjaniEmily R MiraldiClaire A ChougnetDavid A HildemanPublished in: bioRxiv : the preprint server for biology (2023)
Our recent data showed that an aberrant IL-10-producing T follicular helper population (Tfh10) accumulates dramatically with age and is associated with age-related declines in vaccine responsiveness. Through single cell gene expression and chromatin accessibility analysis of IL-10 + and IL-10 âˆ' memory CD4+ T cells from young and aged mice, we identified increased expression of CD153 on aged Tfh and Tfh10 cells. Mechanistically, we linked inflammaging (increased IL-6 levels) to elevated CD153 expression of Tfh cells through c-Maf. Surprisingly, blockade of CD153 in aged mice significantly reduced their vaccine-driven antibody response, which was associated with decreased expression of ICOS on antigen-specific Tfh cells. Combined, these data show that an IL-6/c-Maf/CD153 circuit is critical for maintaining ICOS expression. Thus, although overall Tfh-mediated B cell responses are reduced in the context of vaccines and aging, our data suggest that elevated expression of CD153 on Tfh cells potentiates the remaining Tfh function in aged mice.
Keyphrases
- poor prognosis
- induced apoptosis
- gene expression
- cell cycle arrest
- single cell
- nk cells
- electronic health record
- binding protein
- long non coding rna
- big data
- high fat diet induced
- dna damage
- signaling pathway
- type diabetes
- cell death
- stem cells
- transcription factor
- artificial intelligence
- adipose tissue
- machine learning