TY - JOUR
T1 - Cutting edge
T2 - A thymocyte-thymic epithelial cell cross-talk dynamically regulates intrathymic IL-7 expression in vivo
AU - Alves, Nuno L.
AU - Huntington, Nicholas D.
AU - Mention, Jean Jacques
AU - Richard-Le Goff, Odile
AU - Di Santo, James P.
PY - 2010/6/1
Y1 - 2010/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77953449167&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1000601
DO - 10.4049/jimmunol.1000601
M3 - Article
C2 - 20439914
AN - SCOPUS:77953449167
SN - 0022-1767
VL - 184
SP - 5949
EP - 5953
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -