Cellular Networks of Human Thymic Medullary Stromas Coordinated by p53-Related Transcription Factors
Shingo Ichimiya 1* and Takashi Kojima 1
1 Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan
* To whom correspondence should be addressed. E-mail: ichimiya{at}sapmed.ac.jp.
Submitted on June 7, 2006
Accepted on 20 July 2006
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Abstract |
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The final elimination step of self-reactive T cells occurs in the medulla of the thymus, where a complex framework provided by stromal cells supports an optimal milieu for their selection. Here we present evidence that tight junctions (TJs) widely join medullary stromal cells of the human thymus. Occludin (OCLN) and claudin-1 (CLDN-1) of TJ-associated molecules were dominantly expressed in medullary thymic epithelial cells (mTECs), and that CLDN-4 and CLDN-7 were also localized in some mTECs near Hassall’s corpuscles. Interestingly, p53-like transcription factors were found to up-regulate OCLN and CLDN-1 in human TEC lines, as recently suggested in the regulation of mTEC function. Furthermore, dendritic cells (DCs) of the medulla, with a major role for selection of thymocytes, expressed CLDN-1 and OCLN as well, implying that the interposition of DCs within the mTEC scaffold is also helped by TJs. Analysis of freeze-fracture replicas of the thymus revealed TJ strand structures in the vicinity of gap junction plaques, through which small molecules might move as implied by dye-transfer analysis of a medullary cell line. Thus it is thought that p53-like molecules regulate TJ-associated interactions of medullary stromal cells and that this mechanism might be associated with an intercellular communication network, probably for preserving the medullary niches.
Key Words:
thymus, p63, p73, medulla, tight junction, gap junction, cell communication
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