Faculty Collaboration Database

Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection. Nat Commun 2018 Nov 28;9(1):5037

Date

11/30/2018

Pubmed ID

30487586

Pubmed Central ID

PMC6261948

DOI

10.1038/s41467-018-07492-4

Scopus ID

2-s2.0-85057571059 (requires institutional sign-in at Scopus site)   68 Citations

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.

Author List

Xin G, Zander R, Schauder DM, Chen Y, Weinstein JS, Drobyski WR, Tarakanova V, Craft J, Cui W

Authors

William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Vera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
CD4 Antigens
CD4-Positive T-Lymphocytes
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Immunity, Humoral
Interleukin-10
Interleukins
Mice
Mice, Inbred C57BL
Mice, Knockout
Sequence Analysis, RNA