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

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.

SUBMITTER: Xin G

PROVIDER: S-EPMC6261948 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Single-cell RNA sequencing unveils a unique IL-10-producing T follicular helper subset that sustains humoral immunity during chronic viral infection

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