STAT3 signaling in myeloid cells promotes pathogenic myelin-specific T cell differentiation and autoimmune demyelination

Hsueh Chung Lu, Sunja Kim, Andrew J. Steelman, Kevin Tracy, Beiyan Zhou, Danielle Michaud, Andrew E. Hillhouse, Kranti Konganti, Jianrong Li

Research output: Contribution to journalArticlepeer-review


Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. Dysregulation of STAT3, a transcription factor pivotal to various cellular processes including Th17 cell differentiation, has been implicated in MS. Here, we report that STAT3 is activated in infiltrating monocytic cells near active MS lesions and that activation of STAT3 in myeloid cells is essential for leukocyte infiltration, neuroinflammation, and demyelination in experimental autoimmune encephalomyelitis (EAE). Genetic disruption of Stat3 in peripheral myeloid lineage cells abrogated EAE, which was associated with decreased antigen-specific T helper cell responses. Myeloid cells from immunized Stat3 mutant mice exhibited impaired antigen-presenting functions and were ineffective in driving encephalitogenic T cell differentiation. Single-cell transcriptome analyses of myeloid lineage cells from preclinical wild-type and mutant mice revealed that loss of myeloid STAT3 signaling disrupted antigen-dependent cross-activation of myeloid cells and T helper cells. This study identifies a previously unrecognized requisite for myeloid cell STAT3 in the activation of myelin-reactive T cells and suggests myeloid STAT3 as a potential therapeutic target for autoimmune demyelinating disease.

Original languageEnglish (US)
Pages (from-to)5430-5441
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - Mar 10 2020


  • EAE
  • Multiple sclerosis
  • Myeloid cells
  • STAT3 signaling
  • T cell activation

ASJC Scopus subject areas

  • General


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