Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Xin, Gang; Zander, Ryan; Schauder, David; Chen, Yao; Weinstein, Jason; Drobyski, William; Tarakanova, Vera; Craft, Joseph; Cui, Weiguo
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 14
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-07492-4
• Languages: English
• ISSNs: 2041-1723

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 ofIl10 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. During chronic infection CD4+ T cells can progressively acquire IL-10 producing functionality. Here the authors use single cell RNA sequencing to interrogate the IL10 CD4+ T cell compartment in a murine model of chronic infection and identify Il10-producing Tfh involved in promotion of the antiviral humoral immune response.