Late Breaking Abstract - GATA-3 in lung CD4+T cells drives Interleukin-10 deficiency-induced lung inflammation in asthma

Lung mucosal immunity controls the entrance of infectious agents and allergens into the airways and thus must be tightly regulated. The anti-inflammatory function of Interleukin-10 (IL-10) has been demonstrated in spontaneous Th1-driven colitis in IL-10 deficient mice (IL-10-/-). Allergic asthma is characterized by pathological pulmonary Th2 responses to allergens. Here we investigated the role of IL-10 in lung homeostasis in allergic asthma by analyzing wild type and IL-10 deficient mice in a model of asthma induced by house dust mite (HDM). Targeted deletion of IL-10 resulted in increased lung inflammation, airway mucus production and serum IgE. In further cellular analysis of this lung inflammation we found that IL-10 deficient asthmatic mice had induction of CD4+GATA-3+Th2 cells and SiglecF+CD45.2+CD62L-CD101+inflammatory eosinophils(iEos) as demonstrated by FACS analysis in isolated lung cells of IL-10-/- and WT mice treated with or without HDM. Consistently, the Th2 cytokines IL-4 and IL-13 were found induced in the lung cell supernatants after anti-CD3 and anti-CD28 antibody treatment. Finally, Interleukin-9 (IL-9), a pleiotropic cytokine that influences different target cells involved in allergic asthma, is induced by IL-4 and TGF-beta. Consistently, IL-9 was found induced in the lung cell supernatants of IL-10 deficient mice stimulated with anti CD3 and anti CD28 antibodies. In conclusion, these data indicate that the anti-inflammatory effects of IL-10 in asthma relate to the inhibition of the Th2 transcription factor GATA-3 which results in inhibition of both IL-4 and IL-9. Thus IL-10 is involved in the resolution of allergic asthma by inhibiting GATA-3 expression.