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Minor role of neutrophils in Th17 mediated airway collateral priming towards new antigens

: Albrecht, M.

Allergo-Journal 22 (2013), Nr.6, S.420
ISSN: 0941-8849
Deutscher Allergiekongress (DAK) <8, 2013, Bochum>
Zeitschriftenaufsatz, Konferenzbeitrag
Fraunhofer ITEM ()

We demonstrated earlier that an ongoing Th2 polarized inflammation in the lung facilitates "collateral" inhalational priming to unrelated antigens. Using a mouse model of adoptive T cell transfer, we could show that a Th1 as well as a Th17 polarized lung inflammation also confers collateral priming. Since this phenomenon depends on the presence of IL-17 in both cases, we analyzed the phenotype of the resulting lung inflammation after Th17 mediated collateral priming and investigated the role of neutrophils in this context. Transgenic T cells from DO11.10 mice were polarized to-wards Th17 in vitro and transferred into congenic wildtype mice. After intranasal (i.n.) application of the cognate antigen Ovalbumin (OVA) together with an unrelated antigen, intranasal challenges with either OVA or the unrelated antigen were performed. Neutrophils were depleted in vivo by repeated application of Ly6G-specific antibody (1A8). Lung inflammation was analyzed via assessment of serum antibodies, BAL differentiation, lung histology and analysis of the cytokine profile of mediastinal lymph node and lung cells by means of ELISA and intracellular cytokine staining. The impact of Th17 mediated pulmonary inflammation on lung function was assessed by measuring pulmonary resistance (RL) after repetitive inhalational methacholine (MCh) challenge in orotracheally intubated anesthetized mice. Collateral priming towards unrelated antigens occurred in the context of Th17 polarized lung inflammation, leading to a massive influx of lymphocytes into the lung. Lung function measurements showed that an ongoing Th17 polarized pulmonary inflammation leads to a significant airway hyperresponsiveness (AHR). Depletion of neutrophils during T-cell transfer and primary challenge phase did not influence priming towards unrelated antigens in our model. These results demonstrate a pivotal role for IL-17 producing T cells in conferring inhalational priming and mediating AHR, while indicating a minor role for neutrophils in the collateral priming phase.