Enhanced Th2 cell differentiation and function in the absence of Nox2
Allergy, 2017•Wiley Online Library
Background Patients with chronic granulomatous disease (CGD), whom inherit abnormal
function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as
well as bacterial and fungal infection. There have been studies to reveal the function of Nox2
in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is
still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in
asthma, using various experimental asthma models. Methods Asthma phenotypes were …
function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as
well as bacterial and fungal infection. There have been studies to reveal the function of Nox2
in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is
still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in
asthma, using various experimental asthma models. Methods Asthma phenotypes were …
Background
Patients with chronic granulomatous disease (CGD), whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as well as bacterial and fungal infection. There have been studies to reveal the function of Nox2 in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models.
Methods
Asthma phenotypes were analyzed in response to various allergen‐induced experimental asthma using Nox2‐deficient mice and recombinase gene‐activating‐1‐deficient mice. To understand the underlying mechanisms of exaggerated Th2 effector functions, we investigated the degree of T‐cell activation, levels of activation‐induced cell death (AICD), and regulatory T (Treg)‐cell differentiation in Nox2‐deficient T cells.
Results
Asthma phenotypes were increased through enhanced Th2 differentiation and function in Nox2‐null mice regardless of dose and route of various allergens. Nox2‐deficient T cells also showed hyperactivation, reduced AICD, and diminished Treg‐cell differentiation through increased AKT phosphorylation (T308/S473) and enhanced mitochondrial ROS production.
Conclusion
Our findings indicate that Nox2 deficiency results in exaggerated experimental asthma, which is caused by enhanced Th2 effector function in a T‐cell‐intrinsic manner.
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