Dataset Information

Activin A and TGF-? promote T(H)9 cell-mediated pulmonary allergic pathology.

ABSTRACT:

Background

IL-9-secreting (T(H)9) T cells are thought to represent a distinct T-cell subset. However, evidence for their functionality in disease is uncertain.

Objective

To define a functional phenotype for T(H)9-driven pathology in vivo.

Methods

We used fluorescence-activated cell sorting to identify circulating T(H)9 cells in atopic and nonatopic subjects. In mice we utilized a model of allergic airways disease induced by house dust mite to determine T(H)9 cell function in vivo and the role of activin A in T(H)9 generation.

Results

Allergic patients have elevated T(H)9 cell numbers in comparison to nonatopic donors, which correlates with elevated IgE levels. In a murine model, allergen challenge with house dust mite leads to rapid T(H)9 differentiation and proliferation, with much faster kinetics than for T(H)2 cell differentiation, resulting in the specific recruitment and activation of mast cells. The TGF-? superfamily member activin A replicates the function of TGF-?1 in driving the in vitro generation of T(H)9 cells. Importantly, the in vivo inhibition of T(H)9 differentiation induced by allergen was achieved only when activin A and TGF-? were blocked in conjunction but not alone, resulting in reduced airway hyperreactivity and collagen deposition. Conversely, adoptive transfer of T(H)9 cells results in enhanced pathology.

Conclusion

Our data identify a distinct functional role for T(H)9 cells and outline a novel pathway for their generation in vitro and in vivo. Functionally, T(H)9 cells promote allergic responses resulting in enhanced pathology mediated by the specific recruitment and activation of mast cells in the lungs.

SUBMITTER: Jones CP

PROVIDER: S-EPMC3385370 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Publications

Activin A and TGF-β promote T(H)9 cell-mediated pulmonary allergic pathology.

Jones Carla P CP Gregory Lisa G LG Causton Benjamin B Campbell Gaynor A GA Lloyd Clare M CM

The Journal of allergy and clinical immunology 20120124 4

<h4>Background</h4>IL-9-secreting (T(H)9) T cells are thought to represent a distinct T-cell subset. However, evidence for their functionality in disease is uncertain.<h4>Objective</h4>To define a functional phenotype for T(H)9-driven pathology in vivo.<h4>Methods</h4>We used fluorescence-activated cell sorting to identify circulating T(H)9 cells in atopic and nonatopic subjects. In mice we utilized a model of allergic airways disease induced by house dust mite to determine T(H)9 cell function i ...[more]

PMID: 22277204

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