Cutting edge: A thymocyte-thymic epithelial cell cross-talk dynamically regulates intrathymic IL-7 expression in vivo

Nuno L. Alves, Nicholas D. Huntington, Jean Jacques Mention, Odile Richard-Le Goff, James P. Di Santo

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

Thymic epithelial cells (TECs) are the predominant intrathymic source of the essential thymopoietin IL-7. Whether thymocyte-TEC interactions have a role in the regulation of IL-7 expression is not known. By exploiting IL-7 reporter mice in which yellow fluorescent protein expression identifies TECs expressing high levels of IL-7 (Il7+ TECs), we show that Il7+ TECs segregate from emerging medullary TECs during thymic organogenesis. Although Il7+ TECs normally diminish with age, we found that Il7+ TECs are markedly retained in alymphoid Rag21-/-Il2rg2/2 IL-7 reporter mice that manifest a profound thymopoietic arrest. Transfer of Tcra-/- or wild-type (but not Rag-/-) hematopoietic progenitors to alymphoid IL-7 reporter recipients normalizes the frequency of Il7+ TECs and re-establishes cortical TEC/medullary TEC segregation. Although thymocyte-derived signals are often considered stimulatory forTECmaturation, our findings identify a negative feedback mechanism in which signals derived from TCRb-selected thymocytes modulate TEC-dependent IL-7 expression.

Original languageEnglish
Pages (from-to)5949-5953
Number of pages5
JournalJournal of Immunology
Volume184
Issue number11
DOIs
Publication statusPublished - 1 Jun 2010
Externally publishedYes

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