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@article{Uwadiae:2019:10.1111/all.13602,
author = {Uwadiae, F and Pyle, C and Walker, S and Lloyd, C and Harker, J},
doi = {10.1111/all.13602},
journal = {Allergy},
pages = {650--662},
title = {Targeting the ICOS/ICOS-L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease},
url = {http://dx.doi.org/10.1111/all.13602},
volume = {74},
year = {2019}
}

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TY  - JOUR
AB  - BackgroundAllergic asthma is characterized by chronic inflammation and remodelling of the airways, associated with dysregulated type 2 immune responses and allergenspecific IgE. T follicular helper cells (TFH) are crucial in Tdependent B cell responses and have been implicated in allergic airway disease (AAD). TFH, unlike other CD4+ T cells are uniquely reliant on continuous ICOS signalling to maintain their phenotype after T cell priming, therefore disrupting this signal can impair TFH responses. However, the contribution of TFH to disease during chronic aeroallergen exposure and the therapeutic potential of targeting these cells has not been evaluated.MethodsTo establish AAD, female BALB/c mice were repeatedly exposed to house dust mite or Alternaria alternata three times a week for up to 5 weeks. To examine the impact of TFH on AAD, mice were allergen exposed for 5 weeks and coadministered antiICOSLigand targeted antibodies, 3 times for the last 2 weeks.ResultsTFH were first observed in the lung draining lymph nodes and with further exposure were also found locally within the lungs. TFH accumulated with sustained allergen exposure, alongside germinal centre (GC) B cells. Blockade of ICOS signalling after AAD establishment successfully depleted TFH but did not affect the differentiation of other CD4+ T cell subsets. This reduced GC responses, allergenspecific IgE, inflammation, pulmonary IL13 and airway hyperresponsiveness.ConclusionsTFH are crucial in the regulation of AAD and the ICOS/ICOSL pathway could represent a novel therapeutic target in allergic asthma.
AU  - Uwadiae,F
AU  - Pyle,C
AU  - Walker,S
AU  - Lloyd,C
AU  - Harker,J
DO  - 10.1111/all.13602
EP  - 662
PY  - 2019///
SN  - 0105-4538
SP  - 650
TI  - Targeting the ICOS/ICOS-L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease
T2  - Allergy
UR  - http://dx.doi.org/10.1111/all.13602
UR  - https://onlinelibrary.wiley.com/doi/full/10.1111/all.13602
UR  - http://hdl.handle.net/10044/1/62306
VL  - 74
ER  -

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