Regulation of medullary thymic epithelial cell differentiation and function by the signaling protein Sin. Academic Article uri icon

Overview

abstract

  • Medullary thymic epithelial cells (mTECs) play an important role in T cell tolerance and prevention of autoimmunity. Mice deficient in expression of the signaling protein Sin exhibit exaggerated immune responses and multitissue inflammation. Here, we show that Sin is expressed in the thymic stroma, specifically in mTECs. Sin deficiency led to thymic stroma-dependent autoimmune manifestations shown by radiation chimeras and thymic transplants in nude mice, and associated with defective mTEC-mediated elimination of thymocytes in a T cell receptor transgenic model of negative selection. Lack of Sin expression correlated with a disorganized medullary architecture and fewer functionally mature mTECs under steady-state conditions. Additionally, Sin deficiency inhibited the expansion of mTECs in response to in vivo administration of keratinocyte growth factor (KGF). These results identify Sin as a novel regulator of mTEC development and T cell tolerance, and suggest that Sin is important for homeostatic maintenance of the medullary epithelium in the adult thymus.

publication date

  • April 19, 2010

Research

keywords

  • Phosphoproteins
  • Thymus Gland

Identity

PubMed Central ID

  • PMC2867288

Scopus Document Identifier

  • 77952296464

Digital Object Identifier (DOI)

  • 10.1093/intimm/dxl010

PubMed ID

  • 20404100

Additional Document Info

volume

  • 207

issue

  • 5