Tetramerization of STAT5 promotes autoimmune-mediated neuroinflammation

• DOI: 10.1073/pnas.2116256118
• Publication Date: 2021-12-21T22:55:21Z
• Authors: Kelly L. Monaghan; Drake Aesoph; Amanda G. Ammer; Wen Zheng; Shokofeh Rahimpour; Breanne Y. Farris; Camille A. Spinner; Peng Li; Jian-Xin Lin; Zu-Xi Yu; Vanja Lazarevic; Gangqing Hu; Warren J. Leonard; Edwin C. K. Wan
• Keywords: STAT5

Significance Multiple sclerosis (MS) is an immune-mediated disease that impacts the central nervous system. A murine model of MS, experimental autoimmune encephalomyelitis (EAE), used to determine mechanism MS pathogenesis. STAT5 a transcription factor plays critical role in mediating cellular responses following cytokine stimulation. Activated proteins undergo functional dimerization and tetramerization. This study demonstrates tetramers promote pathogenesis EAE. facilitate interactions between Th17 cells monocyte-derived (MDCs) meninges. In addition, tetramer-mediated expression chemokine CCL17 MDCs promotes cell extravasation Thus, our identified GM-CSF-STAT5 tetramer-CCL17 pathway can be therapeutically targeted.