Journal article
Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection
Nature communications, Vol.9(1), pp.5037-14
11/28/2018
DOI: 10.1038/s41467-018-07492-4
PMCID: PMC6261948
PMID: 30487586
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.
Details
- Title: Subtitle
- Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection
- Creators
- Gang Xin - Versiti Blood Center of WisconsinRyan Zander - Versiti Blood Center of WisconsinDavid M. Schauder - Medical College of WisconsinYao Chen - Medical College of WisconsinJason S. Weinstein - Yale UniversityWilliam R. Drobyski - Medical College of WisconsinVera Tarakanova - Medical College of WisconsinJoseph Craft - Yale UniversityWeiguo Cui - Versiti Blood Center of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.9(1), pp.5037-14
- DOI
- 10.1038/s41467-018-07492-4
- PMID
- 30487586
- PMCID
- PMC6261948
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- Cancer Research Institute Irvington Fellowship Elizabeth Elser Doolittle Postdoctoral Fellowship American Cancer Society (ACS); American Cancer Society R01CA203923 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) AI125741; 5T32HL007209; DK108557; R37AR40072; R21AR068662; P30AR053495; HL126166 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA F30DK108557 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) T32-GM080202 / NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) R01AI125741 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 11/28/2018
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297322602771
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