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Resolution of allergic airway inflammation and airway hyperreactivity is mediated by IL-17-producing {gamma}{delta}T cells

Murdoch, J.R.; Lloyd, C.M.

American Journal of Respiratory and Critical Care Medicine 182(4): 464-476

2010


ISSN/ISBN: 1073-449X
PMID: 20413629
DOI: 10.1164/rccm.200911-1775oc
Accession: 055522601

gammadeltaT lymphocytes are enriched within the epithelial microenvironment, where they are thought to maintain homeostasis and limit immunopathology. gammadeltaT cells are postulated to exert a regulatory influence during acute allergic airway disease, but the mechanism is unknown. Although regulation of allergic airway disease has been attributed to IL-17-producing T helper (Th) 17 cells, we have found that gammadeltaT cells represent the major source of IL-17 in the allergic lung. The aim of this study was to determine the contribution of these IL-17-producing gammadeltaT cells to regulation of allergic airway inflammation. Flow cytometry revealed that IL-17-producing gammadeltaT cells are more prevalent than IL-17(+)alphabetaT cells (Th17) in a murine model of ovalbumin-induced allergic inflammation. Transfer of gammadeltaT cells at the peak of acute allergic responses ameliorated airway hyperresponsiveness with a corresponding acceleration in the resolution of eosinophilic and Th2-driven inflammation. Conversely, functional blockade of gammadeltaT cells led to exacerbation of injury. Neither treatment changed pulmonary Th17 cell numbers. Moreover, transfer of Th17 cells had no effect on disease outcome. Importantly, IL-17-deficient gammadeltaT cells were unable to promote resolution of injury. These data identify IL-17-producing gammadeltaT cells as key regulators of the allergic response in vivo. This unfolds a new perspective for the understanding of gammadeltaT cell function with regard to innate regulation of the adaptive immune responses, emphasizing that resolution of responses are important in determining the outcome of acute inflammatory episodes as well as for maintenance of tissue integrity and homeostasis.

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