Redefining thymus medulla specialization for central tolerance

During &agr;&bgr;T cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3+ T-regulatory cell (T-reg) development. Here, by performing TEC-specific deletion of the thymus medulla regulator lymphotoxin &bgr; receptor (LT&bgr;R), we show that thymic tolerance mechanisms operate independently of LT&bgr;R-mediated mTEC development and organization. Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of intrathymic self-antigens, and support T-reg development despite loss of LT&bgr;R-mediated medulla organogenesis. Moreover, we demonstrate that LT&bgr;R controls thymic tolerance by regulating the frequency and makeup of intrathymic dendritic cells (DCs) required for effective thymocyte negative selection. In all, our study demonstrates that thymus medulla specialization for thymic tolerance segregates from medulla organogenesis and instead involves LT&bgr;R-mediated regulation of the thymic DC pool.

• Publication year

  2017

• Venue

  Journal of Experimental Medicine

• Publication date

  2017-08-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/jem.20171000PMID 28830910PMCID 5679166
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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