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Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception

Authors :
Josephine Poetzsch
Elodie Mohr
Ria Baumgrass
Stefanie Gryzik
Detlef Groth
Yen Hoang
Melanie Venzke
Andreas Hutloff
Timo Lischke
Andreas Radbruch
Isabelle Kadner
Source :
eLife, Vol 9 (2020), eLife
Publication Year :
2020
Publisher :
eLife Sciences Publications Ltd, 2020.

Abstract

Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)". PRI uncovered a subpopulation of IL-21+ IFN-γhigh PD-1low CD40Lhigh CXCR5- Bcl-6- T cells specifically expanded in diseased mice. In addition, these cells express high levels of TNF-α and IL-2, and provide B cell help for IgG production in an IL-21 and CD40L dependent manner. This super-functional T cell subset might be a superior driver of autoimmune processes due to a polyfunctional and high cytokine expression combined with Tfh-like properties.

Details

Language :
English
Volume :
9
Database :
OpenAIRE
Journal :
eLife
Accession number :
edsair.doi.dedup.....6e6696c967686ba26d7bc35c2bd3d838