Activation of gp130 signaling in T cells drives T H 17-mediated multi-organ autoimmunity

• DOI: 10.1126/scisignal.adc9662
• Publication Date: 2024-02-20T18:58:41Z
• Authors: Francis Baumgartner; Stefanos A. Bamop...; Laura Faletti; Hsiang-Jung Hsiao; Maximilian Holz; Irene Gonzalez-Me...; Llorenç Boldo; Arik Horne; Sanket Gosavi; Ceren Özerdem; Nikita Singh; Sven Liebig; Senthilkumar Rama...; Malte Lehmann; Uta Demel; Anja A. Kühl; Tim Wartewig; Jürgen Ruland; Frank T. Wunderlich; Markus Schick; Wolfgang Walther; Stefan Rose-John; Simon Haas; Leticia Quintanil...; Stefan Feske; Stephan Ehl; Rainer Glauben; Ulrich Keller
• Keywords: Glycoprotein 130

The IL-6–gp130–STAT3 signaling axis is a major regulator of inflammation. Activating mutations in the gene encoding gp130 and germline gain-of-function STAT3 (STAT3 GOF ) are associated with multi-organ autoimmunity, severe morbidity, adverse prognosis. To dissect crucial cellular subsets disease biology involved activated signaling, gp130-JAK-STAT3 was constitutively using transgene, L-gp130 , specifically targeted to T cells. cells vivo resulted fatal, early onset, autoimmunity mice that resembled human disease. Female had more rapid progression than male mice. On level, induced activation effector cell differentiation cells, promoted expansion helper type 17 (T H 17) impaired activity regulatory Transcriptomic profiling CD4 + CD8 from these revealed commonly dysregulated genes signature that, when applied transcriptomic data, improved segregation patients transcriptionally diverse healthy controls. findings demonstrate increased gp130-STAT3 leads 17-driven phenotypically resembles