Disruption of Trim9 function abrogates macrophage motility in vivo

作者:Tokarz Debra A; Heffelfinger Amy K; Jima Dereje D; Gerlach Jamie; Shah Radhika N; Rodriguez Nunez Ivan; Kortum Amanda N; Fletcher Ashley A; Nordone Shila K; Law J McHugh; Heber Steffen; Yoder Jeffrey A
来源:Journal of Leukocyte Biology, 2017, 102(6): 1371-1380.
DOI:10.1189/jlb.1A0816-371R

摘要

The vertebrate immune response comprises multiple molecular and cellular components that interface to provide defense against pathogens. Because of the dynamic complexity of the immune system and its interdependent innate and adaptive functionality, an understanding of the whole-organism response to pathogen exposure remains unresolved. Zebrafish larvae provide a unique model for overcoming this obstacle, because larvae are protected against pathogens while lacking a functional adaptive immune system during the first few weeks of life. Zebrafish larvae were exposed to immune agonists for various lengths of time, and a microarray transcriptome analysis was executed. This strategy identified known immune response genes, as well as genes with unknown immune function, including the E3 ubiquitin ligase tripartite motif-9 (Trim9). Although trim9 expression was originally described as "brain specific," its expression has been reported in stimulated human M phi s. In this study, we found elevated levels of trim9 transcripts in vivo in zebrafish M phi s after immune stimulation. Trim9 has been implicated in axonal migration, and we therefore investigated the impact of Trim9 disruption on M phi motility and found that M phi chemotaxis and cellular architecture are subsequently impaired in vivo. These results demonstrate that Trim9 mediates cellular movement and migration in M phi s as well as neurons.

  • 出版日期2017-12