Upregulation of receptor activator of nuclear factor-κB ligand expression in the thymic subcapsular, paraseptal, perivascular, and medullary epithelial cells during thymus regeneration

Abstract

The receptor activator of nuclear factor (NF)-kappaB ligand (RANKL; also termed TRANCE/OPGL/ODF/TNFSF11), a new member of the tumor-necrosis factor (TNF) superfamily, was identified as a key cytokine involved in the differentiation of the immune system and the regulation of immunity as well as in bone metabolism. In particular, RANKL-deficient mice showed defects in the early differentiation of T lymphocytes, suggesting that RANKL is a novel regulator of early thymocyte development. Here, we describe the expression of RANKL during regeneration following acute involution induced by cyclophosphamide in the rat thymus. The present study demonstrates the presence and upregulated expression of the RANKL in thymic subcapsular, paraseptal, perivascular, and medullary epithelial cells during thymus regeneration. Our results suggest that the RANKL expressed in these thymic epithelial cells plays a role in the development of T cells during thymic regeneration.

Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation

“…More recently, KC-derived RANKL was shown to regulate LC activation and UV-induced immunosuppression via an effect on regulatory T cell numbers (10). Moreover, RANKL expression has been described in other epithelia, including mammary glands, lymph nodes, thymus, and thyroid (18,(37)(38)(39), and its role in regulating DC homeostasis and function in these organs should be investigated.…”

RANKL stimulates proliferation, adhesion and IL-7 expression of thymic epithelial cells

“…The mice were used at 8-10 weeks of age and they were given a single intraperitoneal dose of CY (450 mg/kg, Sigma) as described in previous studies (Yoon et al, 1997(Yoon et al, , 2003Lee et al, 2005Lee et al, , 2007. The animals were given RANKL intraperitoneally at a dose of 10 µg per mice.…”

“…It has been well documented that acute thymic involution induced in experimental animals is followed by intensive regeneration after removal of the causative stimuli (Milicevic et al, 1984;Yoon et al, 1997Yoon et al, , 2003Lee et al, 2005Lee et al, , 2007. Cyclophosphamide (CY) exhibits a selective suppressive action on various populations and subpopula-tions of lymphoid cells (Turk and Poulter, 1972;Ozer et al, 1982;Zhu et al, 1987).…”

“…Cyclophosphamide (CY) exhibits a selective suppressive action on various populations and subpopula-tions of lymphoid cells (Turk and Poulter, 1972;Ozer et al, 1982;Zhu et al, 1987). Thus, the application of CY represents a long-established method to induce thymic involution and investigate thymic regeneration (Milicevic et al, 1984;Yoon et al, 1997Yoon et al, , 2003Milicevic and Milicevic, 2004;Lee et al, 2005Lee et al, , 2007. Moreover, CY as well as a number of other agents that induce the acute thymic involution, can be successfully used not only to study the process of regeneration, but also to shed light on the normal thymocytopoiesis, because the changes that occur during the former always mirror the latter process and enable its better understanding (Milicevic and Milicevic, 2004).…”

Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration

“…They were allowed to adjust to their environment for 1 week, and were used at 8-10 weeks of age. Since cyclophosphamide, a DNA alkylating agent commonly used in chemotherapy, is a long-established method of investigating thymic regeneration (Milicévić et al, 1984;Yoon et al, 1997Yoon et al, , 2003Lee et al, 2005Lee et al, , 2007Lee et al, , 2008a, the animals were given a single intraperitoneal dose of cyclophosphamide (400 mg/kg body weight, Sigma) in normal saline, and were killed in groups of four or more at 1, 2, 3, 4, 5, 6, 7 and 10 days after injection. Mice given the same amount of normal saline were used as controls.…”