IL-21R signaling suppresses IL-17+ gamma delta T cell responses and production of IL-17 related cytokines in the lung at steady state and after influenza a virus infection

Emily K. Moser, Jie Sun, Taeg S. Kim, Thomas J. Braciale

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Influenza A virus (IAV) infection of the respiratory tract elicits a robust immune response, which is required for efficient virus clearance but at the same time can contribute to lung damage and enhanced morbidity. IL-21 is a member of the type I cytokine family and has many different immune-modulatory functions during acute and chronic virus infections, although its role in IAV infection has not been fully evaluated. In this report we evaluated the contributions of IL-21/IL-21 receptor (IL-21R) signaling to host defense in a mouse model of primary IAV infection using IL-21R knock out (KO) mice. We found that lack of IL-21R signaling had no significant impact on virus clearance, adaptive T cell responses, or myeloid cell accumulations in the respiratory tract. However, a subset of inflammatory cytokines were elevated in the bronchoalveolar lavage fluid of IL-21R KO mice, including IL-17. Although there was only a small increase in Th17 cells in the lungs of IL-21R KO mice, we observed a dramatic increase in gamma delta (γδ) T cells capable of producing IL-17 both after IAV infection and at steady state in the respiratory tract. Finally, we found that IL-21R signaling suppressed the accumulation of IL-17+ γδ T cells in the respiratory tract intrinsically. Thus, our study reveals a previously unrecognized role of IL-21R signaling in regulating IL-17 production by γδ T cells.

Original languageEnglish (US)
Article numbere0120169
JournalPLoS One
Volume10
Issue number4
DOIs
StatePublished - Apr 7 2015

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Interleukin-21 Receptors
Somatostatin-Secreting Cells
T-cells
Interleukin-17
Virus Diseases
Orthomyxoviridae
Viruses
cytokines
T-lymphocytes
lungs
Cytokines
T-Lymphocytes
Lung
receptors
Influenza A virus
infection
Respiratory System
respiratory system
Knockout Mice
viruses

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

IL-21R signaling suppresses IL-17+ gamma delta T cell responses and production of IL-17 related cytokines in the lung at steady state and after influenza a virus infection. / Moser, Emily K.; Sun, Jie; Kim, Taeg S.; Braciale, Thomas J.

In: PLoS One, Vol. 10, No. 4, e0120169, 07.04.2015.

Research output: Contribution to journalArticle

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