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.
Bibliographical noteFunding Information:
We thank to Myun Soo Kim and Dr. Jung Min Han for many helpful insights and animal care. We appreciate G. Trinchieri and S. Wolf for providing valuable reagents. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2010–0009243).
All Science Journal Classification (ASJC) codes
- Immunology and Allergy