PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients

• DOI: 10.1084/jem.20161427
• Publication Date: 2017-07-14T14:10:23Z
• Authors: Yuan Zhang; Chi A. Ma; Monica G. Lawrence; Timothy J. Break; Michael P. O’Connell; Jonathan J. Lyons; Diego B. López; John S. Barber; Yongge Zhao; Daniel L. Barber; Alexandra F. Freeman; Steven M. Holland; Michail S. Lionakis; Joshua D. Milner
• Keywords: STAT1; Knockout mouse

Patients with hypomorphic mutations in STAT3 and patients hypermorphic STAT1 share several clinical cellular phenotypes suggesting overlapping pathophysiologic mechanisms. We, therefore, examined cytokine signaling CD4+ T cell differentiation these cohorts to characterize common pathways. As expected, of Th17 cells was impaired both cohorts. We found that hyperphosphorylated response stimulation STAT1-dependent PD-L1 up-regulation—known inhibit mouse models—was markedly enhanced as well. Overexpression SOCS3 strongly inhibited phosphorylation up-regulation, diminished expression may lead the observed effects. Defects could be partially overcome vitro via inhibition a model loss-of-function by crossing them PD-1 knockout mice. potential therapeutic target genetic diseases immune deficiency affecting signaling.