The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform
Yousuke Takahama - One of the best experts on this subject based on the ideXlab platform.
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Effects of RANKL on the thymic Medulla.
European journal of immunology, 2011Co-Authors: Izumi Ohigashi, Takeshi Nitta, Enkhsaikhan Lkhagvasuren, Hisataka Yasuda, Yousuke TakahamaAbstract:The thymic Medulla provides a microenvironment where Medullary thymic epithelial cells (mTECs) contribute to the establishment of self-tolerance by the deletion of self-reactive T cells and the generation of regulatory T cells. The progression of thymocyte development critically regulates the optimum formation of the thymic Medulla, as discussed in this article. Of note, it was recently identified that RANKL produced by positively selected thymocytes plays a major role in the thymocyte-mediated Medulla formation. Indeed, transgenic expression of soluble RANKL increased the number of mTECs and enlarged the thymic Medulla in mice. The effects of RANKL on the thymic Medulla may be useful for the engineering of self-tolerance in T cells.
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CCR7-mediated migration of developing thymocytes to the Medulla is essential for negative selection to tissue-restricted antigens.
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Takeshi Nitta, Sachiko Nitta, Martin Lipp, Yousuke TakahamaAbstract:Immature double-positive thymocytes are generated in the thymic cortex, and on positive selection, are induced to differentiate into mature single-positive thymocytes and relocate to the Medulla. CCR7 is pivotal for cortex-to-Medulla migration of positively selected thymocytes, and CCR7-mediated migration to the Medulla is essential for establishing central tolerance, thereby, preventing tissue-specific autoimmunity. However, it was unclear how CCR7-mediated migration to the Medulla affects the establishment of self-tolerance. Here, we show that the deletion of thymocytes specific for insulin-promoter-driven tissue-restricted antigens (TRAs) is significantly impaired in CCR7- or CCR7-ligand-deficient mice. These results indicate that CCR7-mediated migration to the Medulla contributes to the negative selection of TRA-reactive thymocytes.
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ccr7 signals are essential for cortex Medulla migration of developing thymocytes
Journal of Experimental Medicine, 2004Co-Authors: Tomoo Ueno, Martin Lipp, Fumi Saito, Daniel H D Gray, Sachiyo Kuse, Kunio Hieshima, Hideki Nakano, Terutaka Kakiuchi, Richard L Boyd, Yousuke TakahamaAbstract:Upon TCR-mediated positive selection, developing thymocytes relocate within the thymus from the cortex to the Medulla for further differentiation and selection. However, it is unknown how this cortex-Medulla migration of thymocytes is controlled and how it controls T cell development. Here we show that in mice deficient for CCR7 or its ligands mature single-positive thymocytes are arrested in the cortex and do not accumulate in the Medulla. These mutant mice are defective in forming the Medullary region of the thymus. Thymic export of T cells in these mice is compromised during the neonatal period but not in adulthood. Thymocytes in these mice show no defects in maturation, survival, and negative selection to ubiquitous antigens. TCR engagement of immature cortical thymocytes elevates the cell surface expression of CCR7. These results indicate that CCR7 signals are essential for the migration of positively selected thymocytes from the cortex to the Medulla. CCR7-dependent cortex-Medulla migration of thymocytes plays a crucial role in Medulla formation and neonatal T cell export but is not essential for maturation, survival, negative selection, and adult export of thymocytes.
Takeshi Nitta - One of the best experts on this subject based on the ideXlab platform.
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Effects of RANKL on the thymic Medulla.
European journal of immunology, 2011Co-Authors: Izumi Ohigashi, Takeshi Nitta, Enkhsaikhan Lkhagvasuren, Hisataka Yasuda, Yousuke TakahamaAbstract:The thymic Medulla provides a microenvironment where Medullary thymic epithelial cells (mTECs) contribute to the establishment of self-tolerance by the deletion of self-reactive T cells and the generation of regulatory T cells. The progression of thymocyte development critically regulates the optimum formation of the thymic Medulla, as discussed in this article. Of note, it was recently identified that RANKL produced by positively selected thymocytes plays a major role in the thymocyte-mediated Medulla formation. Indeed, transgenic expression of soluble RANKL increased the number of mTECs and enlarged the thymic Medulla in mice. The effects of RANKL on the thymic Medulla may be useful for the engineering of self-tolerance in T cells.
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CCR7-mediated migration of developing thymocytes to the Medulla is essential for negative selection to tissue-restricted antigens.
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Takeshi Nitta, Sachiko Nitta, Martin Lipp, Yousuke TakahamaAbstract:Immature double-positive thymocytes are generated in the thymic cortex, and on positive selection, are induced to differentiate into mature single-positive thymocytes and relocate to the Medulla. CCR7 is pivotal for cortex-to-Medulla migration of positively selected thymocytes, and CCR7-mediated migration to the Medulla is essential for establishing central tolerance, thereby, preventing tissue-specific autoimmunity. However, it was unclear how CCR7-mediated migration to the Medulla affects the establishment of self-tolerance. Here, we show that the deletion of thymocytes specific for insulin-promoter-driven tissue-restricted antigens (TRAs) is significantly impaired in CCR7- or CCR7-ligand-deficient mice. These results indicate that CCR7-mediated migration to the Medulla contributes to the negative selection of TRA-reactive thymocytes.
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the cytokine rankl produced by positively selected thymocytes fosters Medullary thymic epithelial cells that express autoimmune regulator
Immunity, 2008Co-Authors: Yu Hikosaka, Takeshi Nitta, Izumi Ohigashi, Kouta Yano, Yoshio Hayashi, Mitsuru Matsumoto, Joseph M. Penninger, Koichi Matsuo, Naozumi Ishimaru, Hiroshi TakayanagiAbstract:The thymic Medulla provides a microenvironment where Medullary thymic epithelial cells (mTECs) express autoimmune regulator and diverse tissue-restricted genes, contributing to launching self-tolerance. Positive selection is essential for thymic Medulla formation via a previously unknown mechanism. Here we show that the cytokine RANK ligand (RANKL) was produced by positively selected thymocytes and regulated the cellularity of mTEC by interacting with RANK and osteoprotegerin. Forced expression of RANKL restored thymic Medulla in mice lacking positive selection, whereas RANKL perturbation impaired Medulla formation. These results indicate that RANKL produced by positively selected thymocytes is responsible for fostering thymic Medulla formation, thereby establishing central tolerance.
Izumi Ohigashi - One of the best experts on this subject based on the ideXlab platform.
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Effects of RANKL on the thymic Medulla.
European journal of immunology, 2011Co-Authors: Izumi Ohigashi, Takeshi Nitta, Enkhsaikhan Lkhagvasuren, Hisataka Yasuda, Yousuke TakahamaAbstract:The thymic Medulla provides a microenvironment where Medullary thymic epithelial cells (mTECs) contribute to the establishment of self-tolerance by the deletion of self-reactive T cells and the generation of regulatory T cells. The progression of thymocyte development critically regulates the optimum formation of the thymic Medulla, as discussed in this article. Of note, it was recently identified that RANKL produced by positively selected thymocytes plays a major role in the thymocyte-mediated Medulla formation. Indeed, transgenic expression of soluble RANKL increased the number of mTECs and enlarged the thymic Medulla in mice. The effects of RANKL on the thymic Medulla may be useful for the engineering of self-tolerance in T cells.
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the cytokine rankl produced by positively selected thymocytes fosters Medullary thymic epithelial cells that express autoimmune regulator
Immunity, 2008Co-Authors: Yu Hikosaka, Takeshi Nitta, Izumi Ohigashi, Kouta Yano, Yoshio Hayashi, Mitsuru Matsumoto, Joseph M. Penninger, Koichi Matsuo, Naozumi Ishimaru, Hiroshi TakayanagiAbstract:The thymic Medulla provides a microenvironment where Medullary thymic epithelial cells (mTECs) express autoimmune regulator and diverse tissue-restricted genes, contributing to launching self-tolerance. Positive selection is essential for thymic Medulla formation via a previously unknown mechanism. Here we show that the cytokine RANK ligand (RANKL) was produced by positively selected thymocytes and regulated the cellularity of mTEC by interacting with RANK and osteoprotegerin. Forced expression of RANKL restored thymic Medulla in mice lacking positive selection, whereas RANKL perturbation impaired Medulla formation. These results indicate that RANKL produced by positively selected thymocytes is responsible for fostering thymic Medulla formation, thereby establishing central tolerance.
Ihor V. Yosypiv - One of the best experts on this subject based on the ideXlab platform.
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Development of the kidney Medulla.
Organogenesis, 2012Co-Authors: Renfang Song, Ihor V. YosypivAbstract:The mature renal Medulla, the inner part of the kidney, consists of the Medullary collecting ducts, loops of Henle, vasa recta and the interstitium. The unique spatial arrangement of these components is essential for the regulation of urine concentration and other specialized kidney functions. Thus, the proper and timely assembly of Medulla constituents is a crucial morphogenetic event leading to the formation of a functioning metanephric kidney. Mechanisms that direct renal Medulla formation are poorly understood. This review describes the current understanding of the key molecular and cellular mechanisms underlying morphological aspects of Medulla formation. Given that hypoplasia of the renal Medulla is a common manifestation of congenital obstructive nephropathy and other types of congenital anomalies of the kidney and urinary tract (CAKUT), better understanding of how disruptions in Medulla formation are linked to CAKUT will enable improved diagnosis, treatment and prevention of CAKUT and their associated morbidity.
Martin Lipp - One of the best experts on this subject based on the ideXlab platform.
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CCR7-mediated migration of developing thymocytes to the Medulla is essential for negative selection to tissue-restricted antigens.
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Takeshi Nitta, Sachiko Nitta, Martin Lipp, Yousuke TakahamaAbstract:Immature double-positive thymocytes are generated in the thymic cortex, and on positive selection, are induced to differentiate into mature single-positive thymocytes and relocate to the Medulla. CCR7 is pivotal for cortex-to-Medulla migration of positively selected thymocytes, and CCR7-mediated migration to the Medulla is essential for establishing central tolerance, thereby, preventing tissue-specific autoimmunity. However, it was unclear how CCR7-mediated migration to the Medulla affects the establishment of self-tolerance. Here, we show that the deletion of thymocytes specific for insulin-promoter-driven tissue-restricted antigens (TRAs) is significantly impaired in CCR7- or CCR7-ligand-deficient mice. These results indicate that CCR7-mediated migration to the Medulla contributes to the negative selection of TRA-reactive thymocytes.
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ccr7 signals are essential for cortex Medulla migration of developing thymocytes
Journal of Experimental Medicine, 2004Co-Authors: Tomoo Ueno, Martin Lipp, Fumi Saito, Daniel H D Gray, Sachiyo Kuse, Kunio Hieshima, Hideki Nakano, Terutaka Kakiuchi, Richard L Boyd, Yousuke TakahamaAbstract:Upon TCR-mediated positive selection, developing thymocytes relocate within the thymus from the cortex to the Medulla for further differentiation and selection. However, it is unknown how this cortex-Medulla migration of thymocytes is controlled and how it controls T cell development. Here we show that in mice deficient for CCR7 or its ligands mature single-positive thymocytes are arrested in the cortex and do not accumulate in the Medulla. These mutant mice are defective in forming the Medullary region of the thymus. Thymic export of T cells in these mice is compromised during the neonatal period but not in adulthood. Thymocytes in these mice show no defects in maturation, survival, and negative selection to ubiquitous antigens. TCR engagement of immature cortical thymocytes elevates the cell surface expression of CCR7. These results indicate that CCR7 signals are essential for the migration of positively selected thymocytes from the cortex to the Medulla. CCR7-dependent cortex-Medulla migration of thymocytes plays a crucial role in Medulla formation and neonatal T cell export but is not essential for maturation, survival, negative selection, and adult export of thymocytes.
