Citation

BibTex format

@article{Whyte:2022:10.1084/jem.20212391,
author = {Whyte, CE and Singh, K and Burton, OT and Aloulou, M and Kouser, L and Veiga, RV and Dashwood, A and Okkenhaug, H and Benadda, S and Moudra, A and Bricard, O and Lienart, S and Bielefeld, P and Roca, CP and Naranjo-Galindo, FJ and Lombard-Vadnais, F and Junius, S and Bending, D and Ono, M and Hochepied, T and Halim, TYF and Schlenner, S and Lesage, S and Dooley, J and Liston, A},
doi = {10.1084/jem.20212391},
journal = {J Exp Med},
title = {Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits.},
url = {http://dx.doi.org/10.1084/jem.20212391},
volume = {219},
year = {2022}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Interleukin 2 (IL-2) is a key homeostatic cytokine, with therapeutic applications in both immunogenic and tolerogenic immune modulation. Clinical use has been hampered by pleiotropic functionality and widespread receptor expression, with unexpected adverse events. Here, we developed a novel mouse strain to divert IL-2 production, allowing identification of contextual outcomes. Network analysis identified priority access for Tregs and a competitive fitness cost of IL-2 production among both Tregs and conventional CD4 T cells. CD8 T and NK cells, by contrast, exhibited a preference for autocrine IL-2 production. IL-2 sourced from dendritic cells amplified Tregs, whereas IL-2 produced by B cells induced two context-dependent circuits: dramatic expansion of CD8+ Tregs and ILC2 cells, the latter driving a downstream, IL-5-mediated, eosinophilic circuit. The source-specific effects demonstrate the contextual influence of IL-2 function and potentially explain adverse effects observed during clinical trials. Targeted IL-2 production therefore has the potential to amplify or quench particular circuits in the IL-2 network, based on clinical desirability.
AU - Whyte,CE
AU - Singh,K
AU - Burton,OT
AU - Aloulou,M
AU - Kouser,L
AU - Veiga,RV
AU - Dashwood,A
AU - Okkenhaug,H
AU - Benadda,S
AU - Moudra,A
AU - Bricard,O
AU - Lienart,S
AU - Bielefeld,P
AU - Roca,CP
AU - Naranjo-Galindo,FJ
AU - Lombard-Vadnais,F
AU - Junius,S
AU - Bending,D
AU - Ono,M
AU - Hochepied,T
AU - Halim,TYF
AU - Schlenner,S
AU - Lesage,S
AU - Dooley,J
AU - Liston,A
DO - 10.1084/jem.20212391
PY - 2022///
TI - Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits.
T2 - J Exp Med
UR - http://dx.doi.org/10.1084/jem.20212391
UR - https://www.ncbi.nlm.nih.gov/pubmed/35699942
VL - 219
ER -