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Mucosal Immunol. 2017 Mar;10(2):361-372. doi: 10.1038/mi.2016.54. Epub 2016 Jun 22.

Cytokine regulation of lung Th17 response to airway immunization using LPS adjuvant.

Author information

1
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
2
Institute of Infection and Immunity, Cardiff University, Cardiff, UK.

Abstract

Infections caused by bacteria in the airway preferentially induce a Th17 response. However, the mechanisms involved in the regulation of CD4 T-cell responses in the lungs are incompletely understood. Here, we have investigated the mechanisms involved in the regulation of Th17 differentiation in the lungs in response to immunization with lipopolysaccharide (LPS) as an adjuvant. Our data show that both Myd88 and TRIF are necessary for Th17 induction. This distinctive fate determination can be accounted for by the pattern of inflammatory cytokines induced by airway administration of LPS. We identified the production of interleukin (IL)-1β and IL-6 by small macrophages and IL-23 by alveolar dendritic cells (DCs), favoring Th17 responses, and IL-10 repressing interferon (IFN)-γ production. Furthermore, we show that exogenous IL-1β can drastically alter Th1 responses driven by influenza and lymphocytic choriomeningitis virus infection models and induce IL-17 production. Thus, the precision of the lung immune responses to potential threats is orchestrated by the cytokine microenvironment, can be repolarized and targeted therapeutically by altering the cytokine milieu. These results indicate that how the development of Th17 responses in the lung is regulated by the cytokines produced by lung DCs and macrophages in response to intranasal immunization with LPS adjuvant.

PMID:
27328989
PMCID:
PMC5179326
DOI:
10.1038/mi.2016.54
[Indexed for MEDLINE]
Free PMC Article

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