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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Gang Xin, Ryan Zander, David M. Schauder, Yao Chen, Jason S. Weinstein, William R. Drobyski, Vera Tarakanova, Joseph Craft, Weiguo Cui

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. More... »

PAGES

5037

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-07492-4

DOI

http://dx.doi.org/10.1038/s41467-018-07492-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110134146

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30487586


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