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Cutting Edge: A Thymocyte-Thymic Epithelial Cell Cross-Talk Dynamically Regulates Intrathymic IL-7 Expression In Vivo

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 Rag2(-/-)Il2rg(-/-) IL-7 reporter mice that manifest a profound thymopoietic arrest. Transfer of Tcra(-/-) or wild-type (but not Rag2(-/-)) 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 for TEC maturation, our findings identify a negative feedback mechanism in which signals derived from TCRbeta-selected thymocytes modulate TEC-dependent IL-7 expression.
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Submitted on : Monday, January 17, 2022 - 10:27:16 AM
Last modification on : Friday, April 22, 2022 - 11:42:06 AM

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Nuno L Alves, Nicholas D Huntington, Jean-Jacques Mention, Odile Richard Le Goff, James P Di Santo. Cutting Edge: A Thymocyte-Thymic Epithelial Cell Cross-Talk Dynamically Regulates Intrathymic IL-7 Expression In Vivo. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2010, 184 (11), pp.5949 - 5953. ⟨10.4049/jimmunol.1000601⟩. ⟨pasteur-03528198⟩

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