The glycosylation of thymic microenvironments

Paessens, Lutz C.; García-Vallejo, Juan J.; Fernandes, Rosette J.; Kooyk, Yvette van

doi:10.1016/j.imlet.2007.03.005

Cited by 18 publications

(12 citation statements)

References 35 publications

(29 reference statements)

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“…The carboxy-terminal region of chemokines show a high binding affinity for proteoglycans on the vascular endothelium and in the extracellular matrix [27]. Given the abundance of proteoglycans in the IVRs in the thymus [28], serum CCL2 might be deposited inside the IVRs through binding with proteoglycan after tumor development. This assumption is supported by the observation that CCL2 was detected in the IVRs in non-tumor-bearing mice after intravenous injection of recombinant (r) CCL2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Novel Process of Intrathymic Tumor-Immune Tolerance through CCR2-Mediated Recruitment of Sirpα+ Dendritic Cells: A Murine Model

et al. 2012

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Immune surveillance system can detect more efficiently secretory tumor-specific antigens, which are superior as a target for cancer immunotherapy. On the contrary, immune tolerance can be induced in the thymus when a tumor antigen is massively secreted into circulation. Thus, the secretion of tumor-specific antigen may have contradictory roles in tumor immunity in a context-dependent manner. However, it remains elusive on the precise cellular mechanism of intrathymic immune tolerance against tumor antigens. We previously demonstrated that a minor thymic conventional dendritic cell (cDC) subset, CD8α − Sirpα + cDCs, but not the major subset, CD8α + Sirpα − cDCs can selectively capture blood-borne antigens and crucially contribute to the self-tolerance. In the present study, we further demonstrated that Sirpα + cDCs can capture a blood-borne antigen leaking inside the interlobular vascular-rich regions (IVRs). Blood-borne antigen selectively captured by Sirpα + cDCs can induce antigen-specific Treg generation or negative selection, depending on the immunogenicity of the presented antigen. Furthermore, CCR2 expression by thymic Sirpα + cDCs and abundant expression of its ligands, particularly, CCL2 by tumor-bearing mice prompted us to examine the function of thymic Sirpα + cDCs in tumor-bearing mice. Interestingly, tumor-bearing mice deposited CCL2 inside IVRs in the thymus. Moreover, tumor formation induced the accumulation of Sirpα + cDCs in IVRs under the control of CCR2-CCL2 axis and enhanced their capacity to take up antigens, resulting in the shift from Treg differentiation to negative selection. Finally, intrathymic negative selection similarly ensued in CCR2-competent mice once the tumor-specific antigen was secreted into bloodstream. Thus, we demonstrated that thymic Sirpα + cDCs crucially contribute to this novel process of intrathymic tumor immune tolerance.

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Section: Resultsmentioning

confidence: 99%

Novel Process of Intrathymic Tumor-Immune Tolerance through CCR2-Mediated Recruitment of Sirpα+ Dendritic Cells: A Murine Model

et al. 2012

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“…In contrast, our lectin histochemistry results showed that GNA reactive cells were found not only in cortex but also in medulla. Uemura and his colleagues found that, immature thymocytes express a serum mannan-binding protein, which recognizes mannose and GlcNAc (Paessens et al 2007;Kozutsumi et al 1980;Kawasaki et al 1983;Oka et al 1988;Holt et al 1994), identified as an isoform of CD45 molecule with 175 kDa (Uemura et al 1996). Similarly, two mannose bearing bands of 110-212 kDa were determined with our GNA lectin blotting.…”

Section: Discussionmentioning

confidence: 62%

“…In a more recent study, it was suggested that mannose containing structures were found in mainly in the cortex, but not in the medulla (Paessens et al 2007). In contrast, our lectin histochemistry results showed that GNA reactive cells were found not only in cortex but also in medulla.…”

Section: Discussionmentioning

confidence: 95%

The glycosylation status of murin postnatal thymus: a study by histochemistry and lectin blotting

2008

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During the intrathymic development, the fate of the thymocytes depends largely on variable expression of CD4/CD8 markers and T cell receptor protein expressions. In addition, changes of cell surface glycosylation status also affect the thymocyte maturation. In this study the glycosylation alterations in thymic tissues from 1, 9, 13 and 16 days old mice were evaluated by histochemical and lectin blotting techniques. With alcian blue (AB) at pH 5.7/periodic acid-Schiff (PAS) stainings, it was shown that thymic microenvironments contained carboxlylated and sulfated glycosaminoglycans (GAGs). Strong positivity to AB at pH 2.5, which specific for sialomucins, was seen in some medullary thymocytes. Similarly, it was shown that with Maackia amurensis agglutinin (MAL) medullary thymocytes, but not cortical ones, contained alpha(2 --> 3) linked sialic acid structures. On the other hand, while reaction with peanut agglutinin (PNA), which specific for core disaccharide galactose beta(1 --> 3) N-acetylgalactosamine, was only seen in cortical thymocytes, reaction with Galanthus nivalis agglutinin (GNA), which specific for terminal mannose residues, was seen in both cortex and medulla. However, Datura stramonium agglutinin (DSA), which recognizes galactose beta(1 --> 4) N-acetylglucosamine, was not only cell-specific, but it was bound some thymic vessels. With lectin blotting studies, five glycoprotein bands of molecular weights approximately 39, approximately 54, 100, approximately 110 and approximately 212 were found which reacted with MAL, PNA and DSA as well as GNA. These results suggest that glycosylation patterns of cell surface glycoconjugates are modified during thymocyte selection processes of postnatal days.

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“…143 For these reasons, lectins have limited capabilities for in vivo imaging; however, they have been used routinely for imaging glycans ex vivo on cultured cells and on tissue samples. 144,145 …”

Section: Chemical Reporter Strategymentioning

confidence: 99%

Imaging beyond the proteome

Chang

Bertozzi

2012

Chem. Commun.

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Imaging technologies developed in the early 20th century achieved contrast solely by relying on macroscopic and morphological differences between the tissues of interest and the surrounding tissues. Since then, there has been a movement toward imaging at the cellular and molecular level in order to visualize biological processes. This rapidly growing field is known as molecular imaging. In the last decade, many methodologies for imaging proteins have emerged. However, most of these approaches cannot be extended to imaging beyond the proteome. Here, we highlight some of the recently developed technologies that enable imaging of non-proteinaceous molecules in the cell: lipids, signalling molecules, inorganic ions, glycans, nucleic acids, small-molecule metabolites, and protein post-translational modifications such as phosphorylation and methylation.

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The glycosylation of thymic microenvironments

Cited by 18 publications

References 35 publications

Novel Process of Intrathymic Tumor-Immune Tolerance through CCR2-Mediated Recruitment of Sirpα+ Dendritic Cells: A Murine Model

Novel Process of Intrathymic Tumor-Immune Tolerance through CCR2-Mediated Recruitment of Sirpα+ Dendritic Cells: A Murine Model

The glycosylation status of murin postnatal thymus: a study by histochemistry and lectin blotting

Imaging beyond the proteome

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