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  • 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.

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.

PloS one (2015-04-08)
Emily K Moser, Jie Sun, Taeg S Kim, Thomas J Braciale
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Aphidicolin, analytical standard
Sigma-Aldrich
Interleukin-21 from mouse, ≥97% (SDS-PAGE), recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
Sigma-Aldrich
Aphidicolin from Nigrospora sphaerica, ≥98% (HPLC), powder
Sigma-Aldrich
IL-21 human, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
IL-21 human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
7-Amino-1,3-naphthalenedisulfonic acid monopotassium salt monohydrate, BioReagent, suitable for fluorescence, ≥98.0% (T)
Sigma-Aldrich
3,4,4′-Trichlorocarbanilide, 99%