Ongoing research provides further understanding of the biology of RNase A ribonucleases that promote innate immunity with efforts focused toward understanding their mechanisms of action in health and disease. In our major publication on this project, we characterized mouse eosinophil-associated RNase (Ear) 11, a divergent member of the eosinophil ribonuclease cluster, and the only known RNase A family ribonuclease expressed specifically in response to Th2 cytokine stimulation. Mouse Ear 11 is differentially expressed in somatic tissues at baseline; systemic administration of the epithelial cytokine, IL-33, results in 10-5000-fold increased expression in lung and spleen, respectively. Mouse Ear 11 is enzymatically active, although substantially less so than mEar 1 and mEar 2. However, in contrast to RNase 2/EDN and mEar 2, which have been characterized as selective chemoattractants for dendritic cells, mEar 11 has prominent chemoattractant activity for F4/80(+)CD11c(-) tissue macrophages. Chemoattractant activity is not dependent on ribonuclease activity, and requires no interaction with the pattern recognition receptor, Toll-like receptor 2 (TLR2). Taken together, this work characterizes a divergent RNase A ribonuclease with a unique expression pattern and function, and highlights the versatility of this family in promoting innate immunity. Related to this topic, I have contributed an invited review focused on the role of the Eosinophil-derived neurotoxin and its mouse orthologs in promoting host defense (2015, IJMS 16, 15442-15455).
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