TY - JOUR
T1 - Metallophilic macrophages are fully developed in the thymus of autoimmune regulator (Aire)-deficient mice
AU - Milićević, Novica M.
AU - Milićević, Živana Ä
AU - Miljković, Miloš D.
AU - Labudović-Borović, Milica
AU - Laan, Martti
AU - Peterson, Pärt
AU - Kisand, Kai
AU - Scott, Hamish S.
AU - Qu, Ning
AU - Westermann, Jürgen
N1 - Funding Information:
Acknowledgments Thanks are due to Jovanka OgnjanoviT, Sladjana ZoriT and Maire Pihlap for technical assistance. This work was supported by the Ministry for Science and Technological Development of Republic of Serbia (grant no. 145016) and is a part of the Institutional Academic Cooperation between Beograd and Lübeck (project DEU/ 1033146), which is Wnancially supported by the Alexander von Humboldt-Foundation, Bonn, Germany. Martti Laan was supported by Estonian Science Foundation (grant no. 7559).
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/5
Y1 - 2009/5
N2 - Thymic metallophilic macrophages represent a significant component in the thymus physiology. Recently, we showed their presence to be dependent on functional lymphotoxin-β receptor (LTβR) signaling pathway. However, it is unknown whether the development of metallophilic macrophages also requires the Autoimmune regulator (Aire) transcription factor, as suggested by some studies for medullary thymic epithelial cells, or perhaps the presence of Aire-expressing thymic epithelial cells themselves. Therefore, we investigated the presence of metallophilic macrophages in Aire-deficient thymus. Our study shows that the metallophilic macrophages are fully developed in the Aire-deficient thymus; their development is not regulated via Aire transcription factor and does not require the presence of Aire-expressing epithelial cells. On the contrary, in alymphoplasia (ALY) mice (deficient in nuclear factor-kappaB-inducing kinase, NIK), which we used as negative control, thymic metallophilic macrophages are completely lacking, similarly as in LTβR-deficient animals. Together, these results show that the development/maintenance of thymic metallophilic macrophages is executed via LTβR circumventing the Aire transcription factor. Thus, we shed a new light on the molecular requirements for development of these cells and also show that LTβR pathway is a common developmental regulator of metallophilic macrophages in different lymphatic organs (i.e., thymus and spleen).
AB - Thymic metallophilic macrophages represent a significant component in the thymus physiology. Recently, we showed their presence to be dependent on functional lymphotoxin-β receptor (LTβR) signaling pathway. However, it is unknown whether the development of metallophilic macrophages also requires the Autoimmune regulator (Aire) transcription factor, as suggested by some studies for medullary thymic epithelial cells, or perhaps the presence of Aire-expressing thymic epithelial cells themselves. Therefore, we investigated the presence of metallophilic macrophages in Aire-deficient thymus. Our study shows that the metallophilic macrophages are fully developed in the Aire-deficient thymus; their development is not regulated via Aire transcription factor and does not require the presence of Aire-expressing epithelial cells. On the contrary, in alymphoplasia (ALY) mice (deficient in nuclear factor-kappaB-inducing kinase, NIK), which we used as negative control, thymic metallophilic macrophages are completely lacking, similarly as in LTβR-deficient animals. Together, these results show that the development/maintenance of thymic metallophilic macrophages is executed via LTβR circumventing the Aire transcription factor. Thus, we shed a new light on the molecular requirements for development of these cells and also show that LTβR pathway is a common developmental regulator of metallophilic macrophages in different lymphatic organs (i.e., thymus and spleen).
UR - http://www.scopus.com/inward/record.url?scp=64049087991&partnerID=8YFLogxK
U2 - 10.1007/s00418-008-0553-1
DO - 10.1007/s00418-008-0553-1
M3 - Journal articles
C2 - 19148669
AN - SCOPUS:64049087991
SN - 0948-6143
VL - 131
SP - 643
EP - 649
JO - Histochemistry and Cell Biology
JF - Histochemistry and Cell Biology
IS - 5
ER -