Cutting Edge: a thymocyte-thymic epithelial cell cross-talk dynamically regulates intrathymic IL-7 expression in vivo.
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.
Alves
Nuno L
NL
Cytokines and Lymphoid Development Unit, Institut Pasteur, Paris, France.
Huntington
Nicholas D
ND
Mention
Jean-Jacques
JJ
Richard-Le Goff
Odile
O
Di Santo
James P
JP
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D007150:Immunohistochemistry; D015851:Interleukin-7 / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D020239:Receptor Cross-Talk / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology
D015851:Interleukin-7