Is there a glycosaminoglycan-related heterogeneity of the thymic epithelium?

Werneck, Cláudio C.; Cruz, Marcia S.; Silva, Luiz‐Claudio F.; Villa‐Verde, Déa Maria Serra; Savino, Wilson; Mourāo, Paulo A.S.

doi:10.1002/1097-4652(200010)185:1<68::aid-jcp6>3.0.co;2-d

Cited by 23 publications

(5 citation statements)

References 40 publications

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“…Last, it should be noticed that TEC also produce and secrete glycosaminoglycans, including heparan sulfate, and hyaluronic acid, which can also modulate TEC/thymocyte adhesion [53,54].…”

Section: Adhesive Proteinsmentioning

confidence: 99%

Molecular mechanisms governing thymocyte migration: combined role of chemokines and extracellular matrix

Savino

Mendes-da-Cruz

Smaniotto

et al. 2004

Journal of Leukocyte Biology

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Cell migration is crucial for thymocyte differentiation, and the cellular interactions involved now begin to be unraveled, with chemokines, extracellular matrix (ECM) proteins, and their corresponding receptors being relevant in such oriented movement of thymocytes. This notion derives from in vitro, ex vivo, and in vivo experimental data, including those obtained in genetically engineered and spontaneous mutant mice. Thymic microenvironmental cells produce both groups of molecules, whereas developing thymocytes express chemokine and ECM receptors. It is important that although chemokines and ECM proteins can drive thymocyte migration per se, a combined role of these molecules likely concurs for the resulting migration patterns of thymocytes in their various differentiation stages. In this respect, among ECM moieties, there are proteins with opposing functions, such as laminin or fibronectin versus galectin-3, which promote, respectively, adhesion and de-adhesion of thymocytes to the thymic microenvironment. How chemokines and ECM are produced and degraded remains to be more clearly defined. Nevertheless, matrix metalloproteinases (MMPs) likely play a role in the intrathymic ECM breakdown. It is interesting that these molecules also degrade chemokines. Thus, the physiological migration of thymocytes should be conceived as a resulting vector of multiple, simultaneous, or sequential stimuli, involving chemokines, adhesive, and de-adhesive ECM proteins. Moreover, these interactions may be physiologically regulated in situ by matrix MMPs and are influenced by hormones. Accordingly, one can predict that pathological changes in any of these loops may result in abnormal thymocyte migration. This actually occurs in the murine infection by the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. In this model, the abnormal release of immature thymocytes to peripheral lymphoid organs is correlated with the higher migratory response to ECM and chemokines. Lastly, the fine dissection of the mechanisms governing thymocyte migration will provide new clues for designing therapeutic strategies targeting developing T cells. The most important function of the thymus is to generate T lymphocytes, which once leaving the organ, are able to colonize specific regions of peripheral lymphoid organs, the T cell zones, where they can mount and regulate cell-mediated, immune responses. This intrathymic T cell differentiation is a complex sequence of biological events, comprising cell proliferation, differential membrane protein expression, gene rearrangements, massive programmed cell death, and cell migration. In this review, we will focus on the mechanisms involved in controlling the migration of thymocytes, from the entrance of cell precursors into the organ to the exit of mature T cells toward peripheral lymphoid organs. Nevertheless, to better comprehend this issue, it appeared worthwhile to briefly comment on some key aspects of thymocyte differentiation and the tissue context in which it takes place, the thymic microenv...

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“…Last, it should be noticed that TEC also produce and secrete glycosaminoglycans, including heparan sulfate, and hyaluronic acid, which can also modulate TEC/thymocyte adhesion [53,54].…”

Section: Adhesive Proteinsmentioning

confidence: 99%

Molecular mechanisms governing thymocyte migration: combined role of chemokines and extracellular matrix

Savino

Mendes-da-Cruz

Smaniotto

et al. 2004

Journal of Leukocyte Biology

Self Cite

123

124

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“…This meshwork of thymic epithelial cells (e.g., the thymic nurse cells) is essential for the proper development of thymocytes into mature lymphocytes. It was demonstrated that subpopulations of these thymic epithelial cells synthesize diVerent GAGs, some secreting high amounts of DS suggesting that a GAG-related heterogeneity exists (Werneck et al 2000). The presence of various DS domains in lymphoid organs might implicate diVerent functional roles for these domains, e.g., related to growth factor binding.…”

Section: Discussionmentioning

confidence: 99%

Dermatan sulfate domains defined by the novel antibody GD3A12, in normal tissues and ovarian adenocarcinomas

Dam

Yamada

Kobayashi

et al. 2009

Histochem Cell Biol

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Dermatan sulfate (DS) expression in normal tissue and ovarian cancer was investigated using the novel, phage display-derived antibody GD3A12 that was selected against embryonic glycosaminoglycans (GAGs). Antibody GD3A12 was especially reactive with DS rich in IdoA-GalNAc4S disaccharide units. IdoA residues are important for antibody recognition as DS polymers with low numbers of IdoA residues were less reactive, and expression of the DS epimerase in ovarian carcinoma cells was associated with expression of the GD3A12 epitope. Moreover, staining of antibody GD3A12 was abolished by chondroitinase-B lyase digestion. Expression of DS domains defined by antibody GD3A12 was confined to connective tissue of most organs examined and presented as a typical fibrillar-type of staining. Differential expression of the DS epitopes recognized by antibodies GD3A12 and LKN1 (4/2,4 di-O-sulfated DS) was best seen in thymus and spleen, indicating differential expression of various DS domains in these organs. In ovarian carcinomas strong DS expression was found in the stromal parts, and occasionally on tumor cells. Partial co-localization in ovarian carcinomas was observed with decorin, versican and type I collagen suggesting a uniform distribution of this specific DS epitope. This unique anti-DS antibody may be instrumental to investigate the function, expression, and localization of specific DS domains in health and disease.

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“…These cells have a mixed phenotype, expressing cortical and medullary TEC markers (Werneck et al . 2000 ). 2BH4 cells were cultivated in 25 or 75 cm 2 culture flasks with RPMI 1640 medium, supplemented with 10% foetal bovine serum (FBS), 1% L-glutamine, and 40 mg/mL gentamicin (all from Invitrogen, Carlsbad, CA, USA) (designated as complete RPMI medium).…”

Section: Methodsmentioning

confidence: 99%

CXCL12-driven thymocyte migration is increased by thymic epithelial cells treated with prolactin in vitro

et al. 2021

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Is there a glycosaminoglycan-related heterogeneity of the thymic epithelium?

Cited by 23 publications

References 40 publications

Molecular mechanisms governing thymocyte migration: combined role of chemokines and extracellular matrix

Molecular mechanisms governing thymocyte migration: combined role of chemokines and extracellular matrix

Dermatan sulfate domains defined by the novel antibody GD3A12, in normal tissues and ovarian adenocarcinomas

CXCL12-driven thymocyte migration is increased by thymic epithelial cells treated with prolactin in vitro

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