Year: 2018
Type: article
Study design: Case Report
Abstract: OBJECTIVES: is a key immunological transcription factor, with knockout mice studies identifying functional roles in multiple immune cell types. Despite the importance of NFIL3, little is known about its function in humans. METHODS: Here, we characterised a kindred of two monozygotic twin girls with juvenile idiopathic arthritis at the genetic and immunological level, using whole exome sequencing, single cell sequencing and flow cytometry. Parallel studies were performed in a mouse model. RESULTS: The patients inherited a novel p.M170I in NFIL3 from each of the parents. The mutant form of NFIL3 demonstrated reduced stability in vitro. The potential contribution of this mutation to arthritis susceptibility was demonstrated through a preclinical model, where Nfil3-deficient mice upregulated IL-1β production, with more severe arthritis symptoms on disease induction. Single cell sequencing of patient blood quantified the transcriptional dysfunctions present across the peripheral immune system, converging on IL-1β as a pivotal cytokine. CONCLUSIONS: NFIL3 mutation can sensitise for arthritis development, in mice and humans, and rewires the innate immune system for IL-1β over-production.
Source: Annals of the Rheumatic Diseases
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,870
Awards: G1990583613, Practitioner Fellowship, Regulation of Blood Cell Production and Function, Understanding the Immune Response, Develop a mechanistic understanding of how transcriptional and posttranscriptional regulation of gene expression is coordinated by signal transduction pathways., G6160911136, Understanding ILC1 transcriptional regulation and function in immune protection, Immune homeostasis and the immune response, Delineating immune circuits for innate and adaptive immune protection
OpenAlex ID: W2904369547