AIMP1 deficiency enhances airway hyperreactivity in mice via increased T _H2 immune responses

Aminoacyl tRNA synthetase complex-interacting multicomplex protein 1 (AIMP1) is known as a novel cytokine carrying out a variety of biological activities, including angiogenesis and wound repair. In our previous reports AIMP1 was demonstrated to induce T _H1 polarization. However, the effects of AIMP1 deficiency in T _H1 or T _H2 immune disorders remain unclear. In this study, we characterized phenotypes of AIMP1-deficient mice and investigated the role of AIMP1 in T _H2-biased airway hyperreactivity. Clinical signs of allergic airway inflammation were assessed in AIMP1-deficient mice and the effects of AIMP1 deficiency on production of T _H2 cytokines were evaluated in T cells using AIMP1-specific siRNA. Additionally, the enhanced pause values and histologic analysis were assessed in mice receiving AIMP1-deficient CD4 ⁺ T cells with OVA challenge. Clinical signs of spontaneous airway inflammation were noted in AIMP1-deficienct mice. AIMP1-deficient mice showed strongly increased Penh values in response to methacholine without any allergen exposure. Adoptive transfer of AIMP1-deficient CD4 ⁺ T cells to OVA-sensitized C57BL/6 mice exacerbated OVA-induced airway inflammation and increased infiltration of inflammatory cells into the lung. Furthermore, lung DCs in AIMP1-deficient mice showed increased expression of surface molecules, and IL-12p40 level in sera significantly decreased in AIMP1-deficient mice compared to that of wild type mice. These results strongly indicate that AIMP1 plays a role in negatively regulating T _H2 responses in vivo, and AIMP1 can be employed as a novel therapeutic agent against T _H2-biased diseases, particularly asthma.