Stat3 Signaling Promotes Survival And Maintenance Of Medullary Thymic Epithelial Cells

Dakshayani Lomada, Manju Jain, Michelle Bolner, Kaitlin A.G. Reeh, Rhea Kang, Madhava C. Reddy, John DiGiovanni, Ellen R. Richie

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Medullary thymic epithelial cells (mTECs) are essential for establishing central tolerance by expressing a diverse array of self-peptides that delete autoreactive thymocytes and/or divert thymocytes into the regulatory T cell lineage. Activation of the NFκB signaling pathway in mTEC precursors is indispensable for mTEC maturation and proliferation resulting in proper medullary region formation. Here we show that the Stat3-mediated signaling pathway also plays a key role in mTEC development and homeostasis. Expression of a constitutively active Stat3 transgene targeted to the mTEC compartment increases mTEC cellularity and bypasses the requirement for signals from positively selected thymocytes to drive medullary region formation. Conversely, conditional deletion of Stat3 disrupts medullary region architecture and reduces the number of mTECs. Stat3 signaling does not affect mTEC proliferation, but rather promotes survival of immature MHCIIloCD80lo mTEC precursors. In contrast to striking alterations in the mTEC compartment, neither enforced expression nor deletion of Stat3 affects cTEC cellularity or organization. These results demonstrate that in addition to the NFkB pathway, Stat3-mediated signals play an essential role in regulating mTEC cellularity and medullary region homeostasis.

Original languageEnglish (US)
Article numbere1005777
JournalPLoS genetics
Volume12
Issue number1
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Fingerprint Dive into the research topics of 'Stat3 Signaling Promotes Survival And Maintenance Of Medullary Thymic Epithelial Cells'. Together they form a unique fingerprint.

Cite this