CD96 expression determines the inflammatory potential of IL-9–producing Th9 cells

• DOI: 10.1073/pnas.1708329115
• Publication Date: 2018-03-12T19:44:16Z
• Authors: Katarina Stanko; Christina Iwert; Christine Appelt; Katrin Vogt; Julia Schumann; Franziska Janina ...; Stefanie Ahrlich; Stephan Schlickeiser; Chiara Romagnani; Karsten Jürchott; Christian Meisel; Gerald Willimsky; Anja A. Kühl; Birgit Sawitzki
• Keywords: Graft Rejection; Homeodomain Proteins; Inflammation; Male; Mice, Knockout; 0301 basic medicine; Mice, Inbred BALB C; Gene Expression Profiling; Interleukin-9; Dendritic Cells; Skin Transplantation; T-Lymphocytes, Helper-Inducer; Colitis; Mice, Inbred C57BL; Mice; 03 medical and health sciences; PNAS Plus; Antigens, CD; Animals; Humans; Single-Cell Analysis; Cells, Cultured; Signal Transduction

SignificanceT helper type (Th) 9 cells demonstrate both pro- and antiinflammatory properties, pointing to a functional heterogeneity not examined so far. Applying single cell gene expression analysis of alloreactive Th9 cells, we revealed the existence of two major subsets, CD96highand CD96lowTh9 cells, with strongly opposing inflammatory and, especially, colitis-inducing potential. Mechanistically, we found that CD96 controls cytokine and colitis-inducing potential of Th9 cells, providing strong evidence for an inhibitory role of CD96 in controlling CD4+T-cell effector functions. Thus, interfering with CD96-mediated immune inhibition would be a promising approach in preventing Th9-mediated diseases, such as ulcerative colitis, or reinforcement of Th9-mediated immune control of tumors and infections.