Absence of proton-sensing TDAG8 protects against ovalbumin-induced allergic airway inflammation

Abstract

Introduction: The pH of the interstitium and the bronchoalveolar space has been shown to fall in airway inflammatory disease, such as bronchial asthma. Proton-sensing T-cell death associated gene 8 (TDAG8) is mainly expressed in hematopoietic cells. We have previously reported that TDAG8 is a negative regulator for lung neutrophilic inflammation and injury, in part, through the inhibition of chemokine production in the lipopolysaccharide-induced lung injury model. In the allergic airway inflammation, such as bronchial asthma, the role of TDAG8 has not been investigated in detail. Aims: We explored the role of TDAG8 in the allergic airway inflammation with an ovalbumin (OVA)-induced asthma model. Methods: To determine the expression profile of proton-sensing GPCRs, we measured the mRNA expression in lung tissues. TDAG8-deficient (TDAG8-KO) and wild-type (WT) mice were assigned to the following two groups: OVA group, intraperitoneal sensitization and airway challenge with OVA, and control group, those with PBS. Two days after the final challenge, we measured the number of bronchoalveolar lavage (BAL) fluid cells and mRNA expression in lungs. Histological analysis of lung sections was also performed. Results: TDAG8 was expressed in lung tissues. The mRNA expression of TDAG8 and MUC5AC in lungs and eosinophil accumulation in BAL fluids were all increased in OVA group. The OVA-induced eosinophil accumulation and MUC5AC expression in lungs were lower in TDAG8-KO mice than those in WT mice. Conclusions: Our results suggest that absence of TDAG8 protects against OVA-induced allergic airway inflammation and TDAG8 plays an important role in the pathogenesis of asthma.