Metallophilic macrophages are fully developed in the thymus of autoimmune regulator (Aire)-deficient mice
Date
2009
Authors
Milcevic, N.
Milicevic, Z.
Milkovic, M.
Labudovic-Borovic, M.
Laan, M.
Peterson, P.
Kisand, K.
Scott, H.
Qu, N.
Westermann, J.
Editors
Advisors
Journal Title
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Volume Title
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Journal article
Citation
Histochemistry and Cell Biology, 2009; 131(5):643-649
Statement of Responsibility
Novica M. Milićević, Živana Milićević, Miloš D. Miljković, Milica Labudović-Borović, Martti Laan, Pärt Peterson, Kai Kisand, Hamish S. Scott, Ning Qu and Jürgen Westermann
Conference Name
Abstract
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).
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Copyright © Springer-Verlag 2009 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).
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Copyright 2009 Springer-Verlag