Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells

PLoS Genet. 2016 Jan 20;12(1):e1005776. doi: 10.1371/journal.pgen.1005776. eCollection 2016 Jan.

Abstract

Thymic medullary regions are formed in neonatal mice as islet-like structures, which increase in size over time and eventually fuse a few weeks after birth into a continuous structure. The development of medullary thymic epithelial cells (TEC) is dependent on NF-κB associated signaling though other signaling pathways may contribute. Here, we demonstrate that Stat3-mediated signals determine medullary TEC cellularity, architectural organization and hence the size of the medulla. Deleting Stat3 expression selectively in thymic epithelia precludes the postnatal enlargement of the medulla retaining a neonatal architecture of small separate medullary islets. In contrast, loss of Stat3 expression in cortical TEC neither affects the cellularity or organization of the epithelia. Activation of Stat3 is mainly positioned downstream of EGF-R as its ablation in TEC phenocopies the loss of Stat3 expression in these cells. These results indicate that Stat3 meditated signal via EGF-R is required for the postnatal development of thymic medullary regions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Embryonic Development
  • Epithelial Cells*
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / genetics*
  • Flow Cytometry
  • Gene Expression Regulation, Developmental
  • Mice
  • STAT3 Transcription Factor / biosynthesis*
  • STAT3 Transcription Factor / genetics
  • Signal Transduction
  • T-Lymphocytes / metabolism
  • Thymocytes / metabolism
  • Thymus Gland / growth & development
  • Thymus Gland / metabolism

Substances

  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • EGFR protein, mouse
  • ErbB Receptors

Grants and funding

This work was financialy supported by Riken, Japan.The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.