Altered levels of angiogenin and tRNA-derived fragments associate with severe asthma

Recent discoveries highlight angiogenin (ANG) and 5' tRNA-derived fragments as key factors in stress response and cell survival. To explore their role in asthma pathogenesis, particularly in severe cases, we evaluated the levels of ANG and 5' tRNA halves (tRHs) derived from tRNA Glu (5'-tRH Glu: tRF-32-87R8WP9N1EWJM) and tRNA Gly (5'-tRH Gly: tRF-30-PNR8YP9LON4V), two abundant tRHs in the respiratory tract, in sputum and blood samples from asthmatic patients. We found ANG expression is significantly increased in circulating leukocytes from severe asthma patients but not in sputum infiltrates. On the contrary, tRHs levels showed significant alterations only in extracellular compartments. Both tRHs were downregulated in the plasma of asthmatic patients, while elevated 5'-tRH Gly levels were observed in severe sputum samples, indicating tissue-specific roles in disease pathology. Additionally, tRH expression in leukocytes was negatively associated with the disrupted corticosteroid response in asthmatic patients. Altered levels of ANG and 5'-tRH Glu and 5'-tRH Gly were further validated in an in vitro model of pollutant-aggravated, allergen-stimulated macrophages. In summary, our findings provide new insights into the role of ANG and tRHs in asthma pathogenesis, highlighting their potential as novel markers for asthma phenotyping.