Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection

Gang Xin, Ryan Zander (), David M. Schauder, Yao Chen, Jason S. Weinstein, William R. Drobyski, Vera Tarakanova, Joseph Craft and Weiguo Cui ()
Additional contact information
Gang Xin: BloodCenter of Wisconsin
Ryan Zander: BloodCenter of Wisconsin
David M. Schauder: Medical College of Wisconsin
Yao Chen: Medical College of Wisconsin
Jason S. Weinstein: Yale University School of Medicine
William R. Drobyski: Medical College of Wisconsin
Vera Tarakanova: Medical College of Wisconsin
Joseph Craft: Yale University School of Medicine
Weiguo Cui: BloodCenter of Wisconsin

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract During chronic viral infection, the inflammatory function of CD4 T-cells becomes gradually attenuated. Concurrently, Th1 cells progressively acquire the capacity to secrete the cytokine IL-10, a potent suppressor of antiviral T cell responses. To determine the transcriptional changes that underlie this adaption process, we applied a single-cell RNA-sequencing approach and assessed the heterogeneity of IL-10-expressing CD4 T-cells during chronic infection. Here we show an IL-10-producing population with a robust Tfh-signature. Using IL-10 and IL-21 double-reporter mice, we further demonstrate that IL-10+IL-21+co-producing Tfh cells arise predominantly during chronic but not acute LCMV infection. Importantly, depletion of IL-10+IL-21+co-producing CD4 T-cells or deletion of Il10 specifically in Tfh cells results in impaired humoral immunity and viral control. Mechanistically, B cell-intrinsic IL-10 signaling is required for sustaining germinal center reactions. Thus, our findings elucidate a critical role for Tfh-derived IL-10 in promoting humoral immunity during persistent viral infection.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07492-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07492-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07492-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().