RT Journal Article
SR Electronic
T1 Survey of extracellular communication of systemic and organ-specific inflammatory responses through cell free messenger RNA profiling in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.12.14.472685
DO 10.1101/2021.12.14.472685
A1 Jiali Zhuang
A1 Arkaitz Ibarra
A1 Alexander Acosta
A1 Amy P. Karns
A1 Jonathan Aballi
A1 Michael Nerenberg
A1 Stephen R. Quake
A1 Shusuke Toden
YR 2021
UL http://biorxiv.org/content/early/2021/12/16/2021.12.14.472685.abstract
AB Inflammatory and immune responses are essential and dynamic biological processes that protect the body against acute and chronic adverse stimuli. While conventional protein markers have been used to evaluate systemic inflammatory response, the immunological response to stimulation is complex and involves modulation of a large set of genes and interacting signaling pathways of innate and adaptive immune systems. Therefore, there is a need for a non-invasive tool that can comprehensively evaluate and monitor molecular dysregulations associated with inflammatory and immune responses. Here we utilized cell-free messenger RNA (cf-mRNA) RNA-Seq whole transcriptome profiling to assess lipopolysaccharide (LPS) induced and JAK inhibitor modulated inflammatory and immune responses in mouse plasma samples. Considering that, both organspecific recruitment of immune cells and organ resident bespoke immune cells contributes to restoration of organ homeostasis, we also examined LPS-induced gene-expression dysregulation of multiple organs to shed light on organ crosstalk. Cf-mRNA profiling displayed a pattern of systemic immune responses elicited by LPS and dysregulation of associated pathways. Moreover, attenuation of several inflammatory pathways, including STAT and interferon pathways, were observed following the treatment of JAK inhibitor. Lastly, we identified the dysregulation of liverspecific transcripts in cf-mRNA which reflected changes in the gene-expression pattern in this biological compartment. Collectively, using a preclinical model, we demonstrated the potential of plasma cf-mRNA profiling for systemic and organ-specific characterization of drug-induced molecular alterations that are associated with inflammatory and immune responses.Competing Interest StatementJZ, AI, AA, APK, JA, MN, JJS and ST are past/current employees at Molecular Stethoscope Inc. SRQ is a founder of Molecular Stethoscope Inc. and a member of scientific advisory board.