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@article{Glanville:2016:10.1371/journal.ppat.1005913,
author = {Glanville, N and Peel, TJ and Schröder, A and Aniscenko, J and Walton, RP and Finotto, S and Johnston, SL},
doi = {10.1371/journal.ppat.1005913},
journal = {PLOS Pathogens},
title = {Tbet Deficiency Causes T Helper Cell Dependent Airways Eosinophilia and Mucus Hypersecretion in Response to Rhinovirus Infection},
url = {http://dx.doi.org/10.1371/journal.ppat.1005913},
volume = {12},
year = {2016}
}

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TY  - JOUR
AB  - Current understanding of adaptive immune, particularly T cell, responses to human rhinoviruses (RV) is limited. Memory T cells are thought to be of a primarily T helper 1 type, but both T helper 1 and T helper 2 memory cells have been described, and heightened T helper 2/ lessened T helper 1 responses have been associated with increased RV-induced asthma exacerbation severity. We examined the contribution of T helper 1 cells to RV-induced airways inflammation using mice deficient in the transcription factor T-Box Expressed In T Cells (Tbet), a critical controller of T helper 1 cell differentiation. Using flow cytometry we showed that Tbet deficient mice lacked the T helper 1 response of wild type mice and instead developed mixed T helper 2/T helper 17 responses to RV infection, evidenced by increased numbers of GATA binding protein 3 (GATA-3) and RAR-related orphan receptor gamma t (RORγt), and interleukin-13 and interleukin-17A expressing CD4+ T cells in the lung. Forkhead box P3 (FOXP3) and interleukin-10 expressing T cell numbers were unaffected. Tbet deficient mice also displayed deficiencies in lung Natural Killer, Natural Killer T cell and γδT cell responses, and serum neutralising antibody responses. Tbet deficient mice exhibited pronounced airways eosinophilia and mucus production in response to RV infection that, by utilising a CD4+ cell depleting antibody, were found to be T helper cell dependent. RV induction of T helper 2 and T helper 17 responses may therefore have an important role in directly driving features of allergic airways disease such as eosinophilia and mucus hypersecretion during asthma exacerbations.
AU  - Glanville,N
AU  - Peel,TJ
AU  - Schröder,A
AU  - Aniscenko,J
AU  - Walton,RP
AU  - Finotto,S
AU  - Johnston,SL
DO  - 10.1371/journal.ppat.1005913
PY  - 2016///
SN  - 1553-7366
TI  - Tbet Deficiency Causes T Helper Cell Dependent Airways Eosinophilia and Mucus Hypersecretion in Response to Rhinovirus Infection
T2  - PLOS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1005913
UR  - http://hdl.handle.net/10044/1/40871
VL  - 12
ER  -

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