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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Rosenberg, Helene F; Druey, Kirk M (2018) Modeling asthma: Pitfalls, promises, and the road ahead. J Leukoc Biol 104:41-48
Ma, M; Redes, J L; Percopo, C M et al. (2018) Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection. Clin Exp Allergy 48:691-702
Foster, Paul S; Maltby, Steven; Rosenberg, Helene F et al. (2017) Modeling TH 2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunol Rev 278:20-40
Percopo, Caroline M; Brenner, Todd A; Ma, Michelle et al. (2017) SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice. J Leukoc Biol 101:321-328
Kraemer, Laura S; Brenner, Todd A; Krumholz, Julia O et al. (2017) A flow-cytometric method to evaluate eosinophil-mediated uptake of probiotic Lactobacillus reuteri. J Microbiol Methods 137:19-24
Rosenberg, Helene F; Druey, Kirk M (2016) Eosinophils, galectins, and a reason to breathe. Proc Natl Acad Sci U S A 113:9139-41
Yamada, Kelsey J; Barker, Tolga; Dyer, Kimberly D et al. (2015) Eosinophil-associated ribonuclease 11 is a macrophage chemoattractant. J Biol Chem 290:8863-75
Rosenberg, Helene F (2015) Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense. Int J Mol Sci 16:15442-55
Percopo, Caroline M; Dyer, Kimberly D; Ochkur, Sergei I et al. (2014) Activated mouse eosinophils protect against lethal respiratory virus infection. Blood 123:743-52
Yang, Ming; Eyers, Fiona; Xiang, Yang et al. (2014) Expression profiling of differentiating eosinophils in bone marrow cultures predicts functional links between microRNAs and their target mRNAs. PLoS One 9:e97537

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