An essential role of iron in Tfh cell development and effector function

Abstract Background: T follicular helper CD4+ cells (Tfh) are essential for maintenance of systemic lupus erythematosus (SLE) as they help germinal center B generate high affinity auto-antibodies. The activation STAT3 is critical generation Tfh it promotes the transcription BCL6 (the factor cell differentiation). It recognized that activated, proliferating SLE cells, contain more iron than controls. Iron binds CDK1 to accentuate JAK1 phosphorylation and in cells. Whether increased content augments JAK1-STAT3 signaling their differentiation into has not been investigated. Experiments: RNAseq qPCR was used compare regulatory pathways purified from WT SLE-prone mice. Labile (bio-active) measured freshly isolated effect chelator on vitro effector function evaluated. Results: Compared WT, displayed significant increase genes associated with uptake transmembrane transport. gene expression were elevated chelation attenuated activation, IL-21 production generated Conclusion: Our novel data identify an role function. Increased may amplify potentiate differentiation. This can be blocked by restricting free availability. Understanding this aspect biology support strategies control labile potential adjunct therapy. Supported grants Vifor Pharma (P0213104, P0226952) Yogesh Scindia NIH (R01AI135128) Borna Mehrad (R01AI128901) Laurence Morel