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

eLife

Timo Lischke¹  Detlef Groth¹  Andreas Hutloff¹  Yen Hoang²  Elodie Mohr²  Melanie Venzke²  Josephine Poetzsch²  Andreas Radbruch²  Stefanie Gryzik²  Isabelle Kadner²  Ria Baumgrass³ 

[1] University of Potsdam, Potsdam, Germany;German Rheumatism Research Center (DRFZ), A Leibniz Institute, Berlin, Germany;University of Potsdam, Potsdam, Germany;

关键词: autoimmune disease;    cytokine expression;    multi-parametric analysis;    combinatorial protein expression;    cd4+ t cells;    high-dimensional flow cytometry;   

DOI  :  10.7554/eLife.53226

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown