
DOI . ORG {
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Title[redir]:
Depletion of Ift88 in thymic epithelial cells affects thymic synapse and T-cell differentiation in aged mice | Anatomical Science International
Description:
Primary cilia are ubiquitous hair-like organelles, usually projecting from the cell surface. They are essential for the organogenesis and homeostasis of various physiological functions, and their dysfunction leads to a plethora of human diseases. However, there are few reports on the role of primary cilia in the immune system; therefore, we focused on their role in the thymus that nurtures immature lymphocytes to full-fledged T cells. We detected primary cilia on the thymic epithelial cell (TEC) expressing transforming growth factor β (TGF-β) receptor in the basal body, and established a line of an intraflagellar transport protein 88 (Ift88) knockout mice lacking primary cilia in TECs (Ift88-TEC null mutant) to clarify their precise role in thymic organogenesis and T-cell differentiation. The Ift88-TEC null mutant mice showed stunted cilia or lack of cilia in TECs. The intercellular contact between T cells and the “thymic synapse” of medullary TECs was slightly disorganized in Ift88-TEC null mutants. Notably, the CD4- and CD8-single positive thymocyte subsets increased significantly. The absence or disorganization of thymic cilia downregulated the TGF-β signaling cascade, increasing the number of single positive thymocytes. To our knowledge, this is the first study reporting the physiological role of primary cilia and Ift88 in regulating the differentiation of the thymus and T cells.
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Keywords {🔍}
pubmed, article, google, scholar, cas, central, cell, cilia, thymic, cells, primary, synapse, biol, ift, epithelial, university, mice, thymus, intraflagellar, transport, protein, signaling, sci, research, takeda, tgfβ, httpsdoiorgs, differentiation, immunological, cilium, immunol, nat, nature, yamanashi, tcell, mouse, httpsdoiorgjcb, development, required, medicine, japan, privacy, cookies, content, information, science, kutomi, nonaka, human, role,
Topics {✒️}
month download article/chapter ift88-tec null mutant ift88-tec null mutants bardet-biedl syndrome ciliopathy foxn1-cre transgenic mice niemann-pick c1 disease t-cell-antigen recognition stable central accumulation single positive thymocytes discovering cilia-independent functions thymic epithelial cells tgf-β signaling cascade full article pdf thymic epithelial cell article kutomi stinchcombe jc wrong email address pazour gj li mo privacy choices/manage cookies related subjects keratinocyte growth factor english language review takeda science foundation osamu kutomi st designed research thymic cilia downregulated exploratory research center sén takeda cilia protein ift88 β-catenin gene kinesin superfamily proteins cells cilia ciliogenesis thymic environment specific nurtures immature lymphocytes tcr/cd3 complex beech pl spatiotemporal regulations central tolerance tgf-β signaling kif3a–/– mice analysis cd8-positive tgfβ1-induced recruitment normal mhc expression additional information publisher' article log endochondral bone formation intraflagellar transport molecules detected primary cilia t-cell activation
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headline:Depletion of Ift88 in thymic epithelial cells affects thymic synapse and T-cell differentiation in aged mice
description:Primary cilia are ubiquitous hair-like organelles, usually projecting from the cell surface. They are essential for the organogenesis and homeostasis of various physiological functions, and their dysfunction leads to a plethora of human diseases. However, there are few reports on the role of primary cilia in the immune system; therefore, we focused on their role in the thymus that nurtures immature lymphocytes to full-fledged T cells. We detected primary cilia on the thymic epithelial cell (TEC) expressing transforming growth factor β (TGF-β) receptor in the basal body, and established a line of an intraflagellar transport protein 88 (Ift88) knockout mice lacking primary cilia in TECs (Ift88-TEC null mutant) to clarify their precise role in thymic organogenesis and T-cell differentiation. The Ift88-TEC null mutant mice showed stunted cilia or lack of cilia in TECs. The intercellular contact between T cells and the “thymic synapse” of medullary TECs was slightly disorganized in Ift88-TEC null mutants. Notably, the CD4- and CD8-single positive thymocyte subsets increased significantly. The absence or disorganization of thymic cilia downregulated the TGF-β signaling cascade, increasing the number of single positive thymocytes. To our knowledge, this is the first study reporting the physiological role of primary cilia and Ift88 in regulating the differentiation of the thymus and T cells.
datePublished:2022-04-18T00:00:00Z
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headline:Depletion of Ift88 in thymic epithelial cells affects thymic synapse and T-cell differentiation in aged mice
description:Primary cilia are ubiquitous hair-like organelles, usually projecting from the cell surface. They are essential for the organogenesis and homeostasis of various physiological functions, and their dysfunction leads to a plethora of human diseases. However, there are few reports on the role of primary cilia in the immune system; therefore, we focused on their role in the thymus that nurtures immature lymphocytes to full-fledged T cells. We detected primary cilia on the thymic epithelial cell (TEC) expressing transforming growth factor β (TGF-β) receptor in the basal body, and established a line of an intraflagellar transport protein 88 (Ift88) knockout mice lacking primary cilia in TECs (Ift88-TEC null mutant) to clarify their precise role in thymic organogenesis and T-cell differentiation. The Ift88-TEC null mutant mice showed stunted cilia or lack of cilia in TECs. The intercellular contact between T cells and the “thymic synapse” of medullary TECs was slightly disorganized in Ift88-TEC null mutants. Notably, the CD4- and CD8-single positive thymocyte subsets increased significantly. The absence or disorganization of thymic cilia downregulated the TGF-β signaling cascade, increasing the number of single positive thymocytes. To our knowledge, this is the first study reporting the physiological role of primary cilia and Ift88 in regulating the differentiation of the thymus and T cells.
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